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Wang Z, Liao S, Huang Z, Wang J, Wang Y, Yu W, Huang X, Luo M, Lin H, Zhou C. Dietary Effects of Fermented Cottonseed Meal Substituting Fishmeal on the Growth, Biochemical Indexes, Antioxidant Capacity, and Muscle Quality of Juvenile Golden Pompano ( Trachinotus ovatus). AQUACULTURE NUTRITION 2024; 2024:9972395. [PMID: 39555570 PMCID: PMC11208100 DOI: 10.1155/2024/9972395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 04/21/2024] [Accepted: 05/09/2024] [Indexed: 11/19/2024]
Abstract
This study investigated the effects of the dietary replacing fishmeal (FM) with fermented cottonseed meal (FCSM) on growth performance, body coloration, serum biochemistry, muscle quality, and liver antioxidant capacity of juvenile golden pompano (Trachinotus ovatus). Fish were fed with five experimental diets (0 (FM), 12.5% (CSM12.5), 25% (CSM25), 50% (CSM50), and 100% (CSM100) replacement levels) for 8 weeks. The weight gain rate (WGR), specific growth rate (SGR), and condition factor (CF) in fish fed with CSM25 were significantly higher than those of the FM (P < 0.05). ALT, GLU, TG, TC, and LDL of fish fed with CSM100 diet were significantly higher than those in FM (P < 0.05). No significant difference was observed in SOD, CAT, and MDA among all treatments (P > 0.05). The relative gene expression of Nrf2 of fish fed with CSM25 diet was higher than that of the other groups (P < 0.05). The relative gene expression of Keap-1 of fish fed with CSM25 diet was lower than those in FM (P < 0.05). In addition, the replacement of a high proportion of FM with FCSM negatively affect the liver antioxidant capacity of fish. With dietary replacement of FM with FCSM increasing 0%-25%, the relative expressions of GH, myf5, and MSTN were significantly upregulated (P > 0.05). Based on these results, we recommend that of FCSM in the diet of golden pompano, whereas the optimal level of FCSM should be carefully evaluated. In conclusion, the optimum level of dietary replacing FM with FCSM in T. ovatus diet was 24.74%-29.38% based on SGR and WGR.
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Affiliation(s)
- Zhanzhan Wang
- Key Laboratory of Aquatic Product ProcessingMinistry of Agriculture and Rural AffairsSouth China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Guangzhou 510300, China
- School of FisheriesTianjin Agricultural University, Tianjin 300384, China
| | - Shuling Liao
- School of Life ScienceGuangzhou University, Guangzhou 510006, China
| | - Zhong Huang
- Shenzhen Base of South China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Shenzhen 518121, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
| | - Jun Wang
- Key Laboratory of Aquatic Product ProcessingMinistry of Agriculture and Rural AffairsSouth China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Guangzhou 510300, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
| | - Yun Wang
- Key Laboratory of Aquatic Product ProcessingMinistry of Agriculture and Rural AffairsSouth China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Guangzhou 510300, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
| | - Wei Yu
- Shenzhen Base of South China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Shenzhen 518121, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
| | - Xiaolin Huang
- Shenzhen Base of South China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Shenzhen 518121, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
| | - Maoyan Luo
- School of Life ScienceGuangzhou University, Guangzhou 510006, China
| | - Heizhao Lin
- Shenzhen Base of South China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Shenzhen 518121, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
| | - Chuanpeng Zhou
- Key Laboratory of Aquatic Product ProcessingMinistry of Agriculture and Rural AffairsSouth China Sea Fisheries Research InstituteChinese Academy of Fishery Sciences, Guangzhou 510300, China
- Key Laboratory of Efficient Utilization and Processing of Marine Fishery Resources of Hainan ProvinceSanya Tropical Fisheries Research Institute, Sanya 572018, China
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Ding H, You Q, Li D, Liu Y. 5-Demethylnobiletin: Insights into its pharmacological activity, mechanisms, pharmacokinetics and toxicity. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 104:154285. [PMID: 35809375 DOI: 10.1016/j.phymed.2022.154285] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 06/05/2022] [Accepted: 06/17/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND 5-Demethylnobiletin (5DN) is a polymethoxyflavone (PMF) primarily found in citrus fruits. It has various health-promoting properties and hence has attracted significant attention from scholars worldwide. PURPOSE This review is the first to systematically summarize the recent research progress of 5DN, including its pharmacological activity, mechanism of action, pharmacokinetics, and toxicological effects. In addition, the pharmacological mechanism of action of 5DN has been discussed from a molecular biological perspective, and data from in vivo and in vitro animal studies have been compiled to provide a more thorough understanding of 5DN as a potential lead drug. METHODS Data were extracted from SciFinder, PubMed, ScienceDirect and China National Knowledge Infrastructure (CNKI) from database inception to January 2022. RESULTS 5DN has broad pharmacological activities. It exerts anti-inflammatory effects, promotes apoptosis and autophagy, and induces melanogenesis mainly by regulating the JAK2/STAT3, caspase-dependent apoptosis, ROS-AKT/mTOR, MAPK and PKA-CREB signaling pathways. 5DN can be used for treating diseases such as cancer, inflammation-related diseases, rheumatoid arthritis, and neurodegenerative diseases. To date, there have been only a few toxicological studies on 5DN, and both in vitro and in vivo on 5DN have not revealed significant toxic side effects. Pharmacokinetic studies have revealed that the metabolites of 5DN are mainly 5,3'-didemethylnobiletin (M1); 5,4'-didemethylnobiletin (M2) and 5,3',4'-tridemethylnobiletin (M3), in either, glucuronide-conjugated or monomeric form. The pharmacokinetic products of 5DN, especially M1, possess better activity than 5DN for the treatment of cancer. CONCLUSION The anticancer effects of 5DN and its metabolites warrant further investigation as potential drug candidates, especially through in vivo studies. In addition, the therapeutic effects of 5DN in neurodegenerative diseases should be examined in more experimental models, and the absorption and metabolism of 5DN should be further investigated in vivo.
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Affiliation(s)
- Haiyan Ding
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qiang You
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacy, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570100, China
| | - Dan Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Youping Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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D-Carvone Attenuates CCl 4-Induced Liver Fibrosis in Rats by Inhibiting Oxidative Stress and TGF-ß 1/SMAD3 Signaling Pathway. BIOLOGY 2022; 11:biology11050739. [PMID: 35625467 PMCID: PMC9138456 DOI: 10.3390/biology11050739] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/29/2022] [Accepted: 04/28/2022] [Indexed: 12/12/2022]
Abstract
D-carvone is a natural monoterpene found in abundance in the essential oil of aromatic medicinal plants with a wide range of pharmacological values. However, the impact of D-carvone on liver fibrosis remains unclear. This study aimed to evaluate the anti-fibrotic potential of D-carvone in a rat model of liver fibrosis and to clarify the possible underlying mechanisms. Liver fibrosis was induced in rats by carbon tetrachloride, CCl4 (2.5 mL/kg, interperitoneally every 72 h for 8 weeks). Oral treatment of rats with D-carvone (50 mg/kg, daily) started on the 3rd week of CCl4 administration. D-carvone significantly enhanced liver functions (ALT, AST), oxidant/antioxidant status (MDA, SOD, GSH, total antioxidant capacity; TAC), as well as histopathological changes. Moreover, D-carvone effectively attenuated the progression of liver fibrosis, evident by the decreased collagen deposition and fibrosis score by Masson trichrome staining (MT) and α-SMA protein expression. Moreover, D-carvone administration resulted in a significant downregulation of the pro-fibrogenic markers TGF-β1 and SMAD3 and upregulation of MMP9. These findings reveal the anti-fibrotic effect of D-carvone and suggest regulation of the TGF-β1/SMAD3 pathway, together with the antioxidant activity as a mechanistic cassette, underlines this effect. Therefore, D-carvone could be a viable candidate for inhibiting liver fibrosis and other oxidative stress-related hepatic diseases. Clinical studies to support our hypothesis are warranted.
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Effect of silymarin on blood coagulation profile and osmotic fragility in carbon tetrachloride induced hepatotoxicity in male Wistar rats. Toxicol Rep 2022; 9:1325-1330. [DOI: 10.1016/j.toxrep.2022.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/02/2022] [Accepted: 06/06/2022] [Indexed: 11/23/2022] Open
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Chang SN, Kim SH, Dey DK, Park SM, Nasif O, Bajpai VK, Kang SC, Lee J, Park JG. 5-O-Demethylnobiletin Alleviates CCl 4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction. Int J Mol Sci 2021; 22:ijms22031083. [PMID: 33499185 PMCID: PMC7865239 DOI: 10.3390/ijms22031083] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 01/08/2023] Open
Abstract
Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.
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Affiliation(s)
- Sukkum Ngullie Chang
- Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea; (S.N.C.); (D.K.D.); (S.C.K.)
- Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea; (S.H.K.); (S.M.P.)
| | - Se Ho Kim
- Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea; (S.H.K.); (S.M.P.)
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea
| | - Debasish Kumar Dey
- Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea; (S.N.C.); (D.K.D.); (S.C.K.)
| | - Seon Min Park
- Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea; (S.H.K.); (S.M.P.)
| | - Omaima Nasif
- Department of Physiology, College of Medicine, King Saud University (Medical City), King Khalid University Hospital, P.O. Box 2925, Riyadh 11461, Saudi Arabia;
| | - Vivek K. Bajpai
- Department of Energy and Materials Engineering, Dongguk University-Seoul, 30 Pildong-ro 1-gil, Seoul 04620, Korea
- Correspondence: (V.K.B.); (J.T.L.); (J.G.P.); Fax: +82-32-872-4046 (V.K.B.); +82-53-810-4631 (J.L.); +82-54-223-2780 (J.G.P.)
| | - Sun Chul Kang
- Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea; (S.N.C.); (D.K.D.); (S.C.K.)
| | - Jintae Lee
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea
- Correspondence: (V.K.B.); (J.T.L.); (J.G.P.); Fax: +82-32-872-4046 (V.K.B.); +82-53-810-4631 (J.L.); +82-54-223-2780 (J.G.P.)
| | - Jae Gyu Park
- Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea; (S.H.K.); (S.M.P.)
- Correspondence: (V.K.B.); (J.T.L.); (J.G.P.); Fax: +82-32-872-4046 (V.K.B.); +82-53-810-4631 (J.L.); +82-54-223-2780 (J.G.P.)
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Vidičević S, Tošić J, Stanojević Ž, Isaković A, Mitić D, Ristić D, Dekanski D. Standardized Olea europaea L. leaf extract exhibits protective activity in carbon tetrachloride-induced acute liver injury in rats: the insight into potential mechanisms. Arch Physiol Biochem 2020; 126:399-407. [PMID: 30632811 DOI: 10.1080/13813455.2018.1550095] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The protective activity of dry olive leaf extract (DOLE) in carbon tetrachloride (CCl4)-induced liver damage and possible mechanisms involved in this protection were investigated in rats. Acute CCl4 intoxication resulted in a massive hepatic necrosis, in increased serum transaminases, and in a perturbation of oxidative stress parameters in liver tissue [malondyaldehide, glutathione (GSH), catalase]. CCl4 did not affect the expression of caspase-3 and cytochrome c as markers of apoptosis; however, CCl4 increased the AMP-activated protein kinase (AMPK) activity and the expression of autophagy-related protein LC3II and decreased the expression of p62 protein. The pre-treatment with DOLE significantly improved serum markers of liver damage, liver catalase activity, and GSH concentration, suggesting that antioxidative mechanism is responsible for hepatoprotection. Oral administration of DOLE did not influence LC3II conversion and p62 degradation in liver, but AMPK activity was significantly decreased, suggesting the energy balance perturbation as an additional potential mechanism of DOLE hepatoprotective effect.
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Affiliation(s)
- Sašenka Vidičević
- Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Tošić
- Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Željka Stanojević
- Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Isaković
- Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Dragana Mitić
- Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
| | - Dušica Ristić
- Faculty of Biology, University of Belgrade, Belgrade, Serbia
| | - Dragana Dekanski
- Biomedical Research, R&D Institute, Galenika a.d., Belgrade, Serbia
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Natural Chalcones in Chinese Materia Medica: Licorice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:3821248. [PMID: 32256642 PMCID: PMC7102474 DOI: 10.1155/2020/3821248] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 02/07/2020] [Indexed: 12/17/2022]
Abstract
Licorice is an important Chinese materia medica frequently used in clinical practice, which contains more than 20 triterpenoids and 300 flavonoids. Chalcone, one of the major classes of flavonoid, has a variety of biological activities and is widely distributed in nature. To date, about 42 chalcones have been isolated and identified from licorice. These chalcones play a pivotal role when licorice exerts its pharmacological effects. According to the research reports, these compounds have a wide range of biological activities, containing anticancer, anti-inflammatory, antimicrobial, antioxidative, antiviral, antidiabetic, antidepressive, hepatoprotective activities, and so on. This review aims to summarize structures and biological activities of chalcones from licorice. We hope that this work can provide a theoretical basis for the further studies of chalcones from licorice.
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Chen W, Li Y, Hsu CT, Niu CS, Pen WH, Cheng KC, Niu HS. Connective tissue growth factor in hepatocytes is elevated by carbon tetrachloride via STAT3 activation. Mol Med Rep 2020; 21:1390-1398. [PMID: 31922209 DOI: 10.3892/mmr.2020.10916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 11/27/2019] [Indexed: 11/06/2022] Open
Abstract
Carbon tetrachloride (CCl4) is widely used to induce hepatic fibrosis. Therapeutic agents alleviate hepatic fibrosis by inhibiting signal transducer and activator of transcription 3 (STAT3) activation. To understand the direct effects of CCl4 on STAT3 expression in the liver, the present study incubated cultured hepatocytes expressing connective tissue growth factor (CTGF) with CCl4. Rats exposed to CCl4 for 8 weeks exhibited hepatic fibrosis, which was confirmed through the assessment of plasma biomarkers. Isolated liver samples were used to determine the protein levels of CTGF and STAT3 using western blotting. In addition, STAT3 expression was silenced in α mouse liver 12 (AML‑12) cells using small interfering RNA transfection. In addition, a pharmacological inhibitor, stattic, was used to inhibit STAT3 expression. The incubation of AML‑12 cells with CCl4 induced a dose‑dependent increase in CTGF expression and STAT3 activation. Notably, silymarin, an extract from milk thistle, inhibited these changes in AML‑12 cells and the antioxidant tiron produced similar effects. Silencing of STAT3 reduced the CTGF expression promoted by CCl4 in the hepatocytes. Additionally, similar to tiron, stattic inhibited CTGF expression induced by CCl4. In conclusion, CCl4 may activate STAT3 through oxidative stress to promote CTGF expression, which is one of the main factors contributing to the risk of hepatic fibrosis.
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Affiliation(s)
- Wenhsu Chen
- Department of Internal Medicine, E‑Da Hospital, I‑Shou University, Kaohsiung 82401, Taiwan, R.O.C
| | - Yingxiao Li
- Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan
| | - Chao-Tien Hsu
- Department of Pathology, E‑Da Hospital, I‑Shou University, Kaohsiung 82401, Taiwan, R.O.C
| | - Chiang-Shan Niu
- Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan, R.O.C
| | - Wen-Huang Pen
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C
| | - Kai-Chun Cheng
- Pharmacological Department of Herbal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan
| | - Ho-Shan Niu
- Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan, R.O.C
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Tian H, Liu L, Li Z, Liu W, Sun Z, Xu Y, Wang S, Liang C, Hai Y, Feng Q, Zhao Y, Hu Y, Peng J. Chinese medicine CGA formula ameliorates liver fibrosis induced by carbon tetrachloride involving inhibition of hepatic apoptosis in rats. JOURNAL OF ETHNOPHARMACOLOGY 2019; 232:227-235. [PMID: 30471378 DOI: 10.1016/j.jep.2018.11.027] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 11/16/2018] [Accepted: 11/18/2018] [Indexed: 05/28/2023]
Abstract
ETHNOPHARMACOLOGICAL REVELVANCE CGA consisting of Cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin, was demonstrated to be the effective components formula in Fuzheng Huayu (FZHY) capsule, a traditional Chinese medicine approved by China food and drug administration for treatment of liver fibrosis and to inhibit transforming growth factor-β1 (TGF-β1) signaling, previously. AIM OF THE STUDY To evaluate the effects of CGA on hepatic apoptosis in liver fibrosis induced by carbon tetrachloride (CCl4). MATERIALS AND METHODS The hepatic injury and histology was detected by serum biomarker assay and hematoxylin-eosin staining. The hepatic collagen was illustrated by Sirius red staining and hydroxyproline (Hyp) concentration. The hepatic stellate cells (HSCs) activation and hepatic apoptosis was visualized by immunohistochemical analysis of α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling (TUNEL) assay respectively. The protein expression of collagen type I (Col-I), α-SMA, TGF-β1, Fas, tumor necrosis factor receptor 1 (TNF-R1), cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, cleaved-caspase-3, mitochondrial Bcl-2, Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), cytochrome C and cytoplasmic cytochrome C was detected by western-blot. RESULTS CGA or FZHY ameliorated liver histological changes, decreasing serum alanine aminotransferase, aspartate aminotransferase, hepatic Hyp, TUNEL positive-stained area, and down-regulated the protein expression of α-SMA, TGF-β1, Col-I, Fas, TNF-R1, cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, and cleaved-caspase-3, mitochondrial Bax, Bak, and cytoplasmic cytochrome C, while restored the expression of mitochondrial Bcl-2 and cytochrome C. CONCLUSION CGA formula ameliorates liver fibrosis induced by CCl4, which is correlated to its inhibition on hepatic apoptosis.
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Affiliation(s)
- Huajie Tian
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Lin Liu
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Zhixiong Li
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
| | - Wei Liu
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Zhaolin Sun
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
| | - Yongbin Xu
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Shunchun Wang
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Chungeng Liang
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Yamei Hai
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Qin Feng
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Yu Zhao
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Yiyang Hu
- Institute of Clinical Pharmacology, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China.
| | - Jinghua Peng
- Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China.
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Gao Y, Fang L, Wang X, Lan R, Wang M, Du G, Guan W, Liu J, Brennan M, Guo H, Brennan C, Zhao H. Antioxidant Activity Evaluation of Dietary Flavonoid Hyperoside Using Saccharomyces Cerevisiae as a Model. Molecules 2019; 24:molecules24040788. [PMID: 30813233 PMCID: PMC6412469 DOI: 10.3390/molecules24040788] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 02/19/2019] [Accepted: 02/21/2019] [Indexed: 02/08/2023] Open
Abstract
Oxidative stress leads to various diseases, including diabetes, cardiovascular diseases, neurodegenerative diseases, and even cancer. The dietary flavonol glycoside, hyperoside (quercetin-3-O-galactoside), exerts health benefits by preventing oxidative damage. To further understand its antioxidative defence mechanisms, we systemically investigated the regulation of hyperoside on oxidative damage induced by hydrogen peroxide, carbon tetrachloride, and cadmium in Saccharomyces cerevisiae. Hyperoside significantly increased cell viability, decreased lipid peroxidation, and lowered intracellular reactive oxygen species (ROS) levels in the wild-type strain (WT) and mutants gtt1∆ and gtt2∆. However, the strain with ctt1∆ showed variable cell viability and intracellular ROS-scavenging ability in response to the hyperoside treatment upon the stimulation of H2O2 and CCl4. In addition, hyperoside did not confer viability tolerance or intercellular ROS in CdSO4-induced stress to strains of sod1∆ and gsh1∆. The results suggest that the antioxidative reactions of hyperoside in S. cerevisiae depend on the intercellular ROS detoxification system.
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Affiliation(s)
- Yuting Gao
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Lianying Fang
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Xiangxing Wang
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Ruoni Lan
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Meiyan Wang
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Gang Du
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Wenqiang Guan
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Jianfu Liu
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
| | - Margaret Brennan
- Centre for Food Research and Innovation, Department of Wine, Food and Molecular Bioscience, Lincoln University, Lincoln 7647, New Zealand.
| | - Hongxing Guo
- The Third Central Clinical College, Tianjin Medical University, Jintang Road, Hedong, Tianjin 300170, China.
| | - Charles Brennan
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
- Centre for Food Research and Innovation, Department of Wine, Food and Molecular Bioscience, Lincoln University, Lincoln 7647, New Zealand.
| | - Hui Zhao
- Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
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11
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Zhou Y, Li P, Fan N, Wang X, Liu X, Wu L, Zhang W, Zhang W, Ma C, Tang B. In situ visualization of peroxisomal peroxynitrite in the livers of mice with acute liver injury induced by carbon tetrachloride using a new two-photon fluorescent probe. Chem Commun (Camb) 2019; 55:6767-6770. [DOI: 10.1039/c9cc02483b] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In situ visualization of peroxisomal peroxynitrite in the livers of mice with acute liver injury using a new two-photon fluorescent probe.
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Affiliation(s)
- Yongqing Zhou
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Ping Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Nannan Fan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Xin Wang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Xiaoning Liu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Lijie Wu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Wen Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Wei Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
| | - Changle Ma
- College of Life Sciences, Shandong Normal University
- Jinan 250014
- P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University
- Jinan 250014
- People's Republic of China
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12
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Essawy AE, Abdel-Wahab WM, Sadek IA, Khamis OM. Dual protective effect of ginger and rosemary extracts against CCl 4-induced hepatotoxicity in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2018; 25:19510-19517. [PMID: 29730760 DOI: 10.1007/s11356-018-2129-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 04/24/2018] [Indexed: 06/08/2023]
Abstract
The present study aimed to investigate the protective effect of aqueous extracts of ginger (GE) and rosemary (RE), both individually and in combination, on carbon tetrachloride (CCl4)-induced liver injury in adult male rats. CCl4 induced significant increase in liver enzymes, bilirubin, triglycerides, and total cholesterol while total protein, albumin, and globulin were significantly decreased. Also, the activity of cytochrome P450 (CYP) and oxidative stress markers were found to be elevated with a concomitant decrease in the activity of antioxidant enzymes in hepatic tissue. Supplementation with extracts of ginger or rosemary effectively relieved most of the CCl4-induced alterations when administered singly. The joint therapy of the two extracts was more effective. The histological investigation strongly confirmed the highly protective effect of the two plant extracts in the hepatocytes. These findings suggest that rosemary and ginger extracts are effective in improving both the function and structure of the hepatocytes through their potent antioxidant effect and point out to the possibility of using a combination of both as an adjunct therapy in liver diseases.
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Affiliation(s)
- Amina E Essawy
- Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt
| | - Wessam M Abdel-Wahab
- Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt.
- Department of Basic Sciences/Biology Unit, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, P.O. Box 2114, Dammam, 31451, Saudi Arabia.
| | - Ismail A Sadek
- Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt
| | - Omnia M Khamis
- Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt
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13
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Alam MF, Safhi MM, Anwer T, Siddiqui R, Khan G, Moni SS. Therapeutic potential of Vanillylacetone against CCl 4 induced hepatotoxicity by suppressing the serum marker, oxidative stress, inflammatory cytokines and apoptosis in Swiss albino mice. Exp Mol Pathol 2018; 105:81-88. [PMID: 29909158 DOI: 10.1016/j.yexmp.2018.06.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 05/31/2018] [Accepted: 06/13/2018] [Indexed: 12/22/2022]
Abstract
The aim of this research was to investigate the therapeutic potential of Vanillylacetone against carbon tetrachloride (CCl4) induced hepatotoxicity in mice through understanding the serum marker, oxidative stress mechanism and cytokine networks. Carbon tetrachloride is highly hepatotoxic used as research based on animal model. The mice were classified into five groups and each had eight mice. Group-I was controlled and the vehicle was given orally. Group-II was toxic and carbon tetrachloride (1.5 ml/kg) twice a week for 15 days was administered by intra-peritoneal injections. Group- III and IV were pre-treated with Vanillylacetone 50 & 100 mg kg-1 body weight given every day p.o. while, Group-V received only Vanillylacetone (100 mg kg-1 body weight) for 15 days orally. The finding indicates that the administration of CCl4 causes significant elevation of enzyme markers, oxidative stress, inflammatory cytokine and apoptotic markers in Group-II as compared to Group-I. The administration of Vanillylacetone (50 and100 mg kg-1) significantly suppresses the elevated serum enzymes, oxidative stress (TBARS), an inflammatory cytokine (IL2 and TNFα) and apoptotic markers (Caspase-3 and 9) in Group-III and IV as compared to Group-II. It was also noticed that the higher dose of Vanillylacetone (100 mg) is more effective than lower dose of Vanillylacetone (50 mg). There were no significant changes observed with higher dose of Vanillylacetone (100 mg kg-1) in Group-V as compared to Group-I. Histopathological analysis also supported the above findings. Overall, this results shows that Vanillylacetone has a good antioxidant and therapeutic properties which can help in preventing the chemically (CCl4) induced hepatotoxicity.
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Affiliation(s)
- Mohammad Firoz Alam
- Neuroscience and Toxicology Unit, Pharmacology & Toxicology Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia.
| | - Mohammed M Safhi
- Neuroscience and Toxicology Unit, Pharmacology & Toxicology Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia
| | - Tarique Anwer
- Neuroscience and Toxicology Unit, Pharmacology & Toxicology Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia
| | - Rahimullah Siddiqui
- Neuroscience and Toxicology Unit, Pharmacology & Toxicology Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia
| | - Gyas Khan
- Division of Pharmaceutical Biotechnology, Pharmaceutics Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia
| | - Sivakumar Sivagurunathan Moni
- Division of Pharmaceutical Biotechnology, Pharmaceutics Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia
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14
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Phenolic compounds from Syzygium jambos (Myrtaceae) exhibit distinct antioxidant and hepatoprotective activities in vivo. J Funct Foods 2018. [DOI: 10.1016/j.jff.2017.12.055] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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15
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Sang L, Wang XM, Xu DY, Sang LX, Han Y, Jiang LY. Morin enhances hepatic Nrf2 expression in a liver fibrosis rat model. World J Gastroenterol 2017; 23:8334-8344. [PMID: 29307993 PMCID: PMC5743504 DOI: 10.3748/wjg.v23.i47.8334] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 10/20/2017] [Accepted: 11/14/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2 (Nrf2) signaling pathway.
METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride (CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimens were obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin (α-SMA), collagen I, collagen III, Nrf2, heme oxygenase (HO-1), and quinone oxidoreductase 1 (NQO1) using frozen liver specimens.
RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower mRNA and protein expression of α-SMA, collagen I, and collagen III, but significantly higher mRNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only (P < 0.05).
CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors (HO-1 and NQO1) and reducing the expression of α-SMA, collagen I, and collagen III in CCl4-induced liver fibrosis rats.
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Affiliation(s)
- Liang Sang
- Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Xue-Mei Wang
- Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Dong-Yang Xu
- Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Yang Han
- Department of Pathology, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Long-Yang Jiang
- Pharmacy College, China Medical University, Shenyang 110001, Liaoning Province, China
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16
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Hepatoprotective Effect of Microemulsion-Based System of Prunus Cerasus Kernel Extract on CCL4-induced Liver Damage in Mice. Jundishapur J Nat Pharm Prod 2017. [DOI: 10.5812/jjnpp.14282] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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17
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Zhao J, Zhang Y, Wan Y, Hu H, Hong Z. Pien Tze Huang Gan Bao attenuates carbon tetrachloride‑induced hepatocyte apoptosis in rats, associated with suppression of p53 activation and oxidative stress. Mol Med Rep 2017; 16:2611-2619. [PMID: 28713991 PMCID: PMC5547969 DOI: 10.3892/mmr.2017.6936] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 04/12/2017] [Indexed: 01/10/2023] Open
Abstract
Pien Tze Huang Gan Bao (PZH-GB), a traditional Chinese medicine, has been used for thousands of years as a protective remedy effective against liver injury induced by excessive alcohol and smoking. The present study aimed to evaluate the protective effects and potential mechanisms of PZH-GB against carbon tetrachloride (CCl4)-induced hepatic injury. Rats were pre-treated with silymarin (50 mg/kg) or different doses of PZH-GB (150, 300 or 600 mg/kg) orally administered for 7 days. At the end of treatment, the rats were intraperitoneally injected with CCl4, or control rats received a corn oil injection. The lactate dehydrogenase (LDH) levels in serum were evaluated. Apoptosis was assessed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. p53, B-cell lymphoma 2 (Bcl-2), B cell-lymphoma 2-associated X protein (Bax), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1) were measured by reverse transcription-quantitative polymerase chain reaction and western blotting. The activity of caspase-9 and caspase-3 were measured by a colorimetric assay. The results indicated that silymarin and PZH-GB prevented CCl4-induced serum LDH elevations, and CCl4 induced high levels of LDH. Compared with the CCl4 group, silymarin and PZH-GB treatment significantly decreased LDH levels. Histopathological results revealed that silymarin and PZH-GB ameliorated the CCl4-induced liver histological alterations. The TUNEL results showed that compared with the control group, CCl4 induced liver cell apoptosis, while silymarin and PZH-GB treatment inhibited apoptosis and the TUNEL-positive cells. The elevated expression of Bax, p53, iNOS, COX-2 and CYP2E1 were reduced by silymarin or PZH-GB pretreatment, whereas reduced Bcl-2 expression levels were increased. CCl4 increased the activity of caspase-9 and −3 by 6.86- and 7.42-fold, respectively; however, silymarin and PZH-GB ameliorated this effect. In conclusion, silymarin and PZH-GB treatment prevented the deleterious effects on liver functions by attenuation of oxidative stress, inflammation and mitochondrial apoptosis via the p53 signaling pathway.
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Affiliation(s)
- Jinyan Zhao
- Biomedical Research Center, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Yuchen Zhang
- Biomedical Research Center, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Yun Wan
- Biomedical Research Center, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Haixia Hu
- Biomedical Research Center, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Zhenfeng Hong
- Biomedical Research Center, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
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18
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Kumar S, Wang J, Shanmukhappa SK, Gandhi CR. Toll-Like Receptor 4-Independent Carbon Tetrachloride-Induced Fibrosis and Lipopolysaccharide-Induced Acute Liver Injury in Mice: Role of Hepatic Stellate Cells. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 187:1356-1367. [PMID: 28412299 PMCID: PMC5455062 DOI: 10.1016/j.ajpath.2017.01.021] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 01/30/2017] [Indexed: 12/29/2022]
Abstract
Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is implicated in acute and chronic liver injury; its effects are mediated predominantly via the membrane receptor Toll-like receptor 4 (TLR4). However, TLR4-independent effects of LPS may play important role in hepatic pathophysiology. We investigated carbon tetrachloride (CCl4)-induced fibrosis and LPS-induced acute liver injury in wild-type (WT) and B6.B10ScN-Tlr4lps-del/JthJ [TLR4-knockout (KO)] mice. Effects of LPS on fibrogenic hepatic stellate cells (HSCs) from WT and TLR4-KO mice were assessed in vitro. CCl4 produced similar fibrosis and necroinflammation and increased the mRNA and protein expression of cytokines and chemokines in WT and TLR4-KO mice. However, circulating LPS concentration did not increase in CCl4-treated mice. Interestingly, LPS down-modulated α-smooth muscle actin (activated HSC marker) and collagen 1 in both WT and TLR4-KO HSCs. LPS induced similar activation of NF-κB, and stimulated the expression of cytokines and chemokines in WT and TLR4-KO HSCs. Finally, LPS caused similar inflammation and injury in previously untreated WT and TLR4-KO mice. The results provide evidence of the TLR4/LPS-independent mechanisms of liver fibrosis and also indicate that TLR4 is not entirely critical to LPS-induced acute liver injury. The results further indicate that LPS signaling in activated HSCs might be a mechanism of limiting liver fibrosis.
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Affiliation(s)
- Sudhir Kumar
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cincinnati VA Medical Center, Cincinnati, Ohio; Department of Surgery, University of Cincinnati, Cincinnati, Ohio
| | - Jiang Wang
- Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Shiva Kumar Shanmukhappa
- Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Chandrashekhar R Gandhi
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Cincinnati VA Medical Center, Cincinnati, Ohio; Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
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Ratha P, Chitra L, Ancy I, Kumaradhas P, Palvannan T. New amino acid-Schiff base derived from s-allyl cysteine and methionine alleviates carbon tetrachloride-induced liver dysfunction. Biochimie 2017; 138:70-81. [PMID: 28454919 DOI: 10.1016/j.biochi.2017.04.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 04/09/2017] [Accepted: 04/22/2017] [Indexed: 12/22/2022]
Abstract
In spite of the tremendous stride in modern medicine, conventional drugs used in the hepatotoxic management are mostly inadequate. The present study aims in the synthesis of novel Schiff base compound derived using s-allyl cystiene and methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1-carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was characterized using UV-visible spectrophotometer, FTIR, 1HNMR, and GC-MS. ACEMB showed potent in vitro antioxidant property. Chronic administration of ACEMB prior to CCl4 intoxication: i) attenuated the leakage of liver injury markers, such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into the blood circulation; ii) normalized the concentration of total proteins, albumin and globulin to control level; and iii) protected the liver against dyslipidemia. These effects of ACEMB show the preservation of endoplasmic reticulum function against CCl4 toxicity in the liver. The protective effect of ACEMB was due to its antioxidant property, which was revealed by reduced oxidative stress (TBARS and HP) and enhanced functions of the endogenous antioxidative system (SOD, catalase, GPx, GST, GSH, vitamin E and C) against CCl4 intoxication. Also, ACEMB protected the functional activities of the various mitochondrial tricarboxylic acid cycle and oxidative phosphorylation enzymes. The biochemical alterations are in concurrence with the histological observations, wherein ACEMB pretreatment prevented the vacuolation, degeneration of nuclei and necrosis of hepatocytes. In addition, in silico analysis reveals the interaction of ACEMB in the active site of cytochrome P450. ACEMB mediates hepatoprotective effect by substituting itself as an antioxidant and decreasing oxidative stress, thereby diminishing the intracellular organelle dysfunction against CCl4 toxicity in the liver.
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Affiliation(s)
- Periyasamy Ratha
- Department of Biochemistry, Periyar University, Salem, Tamil Nadu 636011, India
| | - Loganathan Chitra
- Department of Biochemistry, Periyar University, Salem, Tamil Nadu 636011, India
| | - Iruthayaraj Ancy
- Department of Physics, Periyar University, Salem, Tamil Nadu 636011, India
| | - Poomani Kumaradhas
- Department of Physics, Periyar University, Salem, Tamil Nadu 636011, India
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Zou L, Chen S, Li L, Wu T. The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. ACTA ACUST UNITED AC 2017; 69:451-460. [PMID: 28434817 DOI: 10.1016/j.etp.2017.04.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 03/15/2017] [Accepted: 04/03/2017] [Indexed: 01/12/2023]
Abstract
CONTEXT Hyperoside was used to treat cardiovascular disease for many years in China. It was shown great effect on regulation of lipid metabolism. But there is lack of reports about the effects of hyperoside on liver diseases. OBJECTIVE This study was designed to investigate the potentially protective effects of hyperoside and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation on Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. MATERIALS AND METHODS All mice were divided into six groups containing 6 animals per group. Mice in different group were given relative processing for 4 weeks. The potentially protective effects of hyperoside on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. RESULTS CCl4 administration caused a marked increase in the levels of serum aminotransferases, serum monoamine oxidase (MAO) and lipid peroxidation, MAO in mouse liver homogenates. Also decreased activities of cellular antioxidant defense enzymes were found after CCl4 exposure. Histopathological changes induced by CCl4 including regenerative nodules, deteriorated parenchyma. Hyperoside and silymarin reduced these changes and attenuated the pathological effects of CCl4 induced liver injury. In addition, hyperoside exhibited antioxidant effects in vitro. In Western blot analysis, the protein level of Nrf2 was downregulated after CCl4 administration and reversed by hyperoside. CONCLUSION Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl4-induced liver fibrosis mice.
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Affiliation(s)
- Liyi Zou
- School of Pharmacy, Guangdong Medical University, Dongguan 523-808, China
| | - Shaoru Chen
- State key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Li Li
- Dongguan Scientific Research Center, Guangong Medical University, Dongguan, Guangdong, 523-808, China.
| | - Tie Wu
- School of Pharmacy, Guangdong Medical University, Dongguan 523-808, China.
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Coballase-Urrutia E, Cárdenas-Rodríguez N, González-García MC, Núñez-Ramírez E, Floriano-Sánchez E, González-Trujano ME, Fernández-Rojas B, Pedraza-Chaverrí J, Montesinos-Correa H, Rivera-Espinosa L, Sampieri AIII, Carmona-Aparicio L. Biochemical and molecular modulation of CCl 4-induced peripheral and central damage by Tilia americana var. mexicanaextracts. Saudi Pharm J 2017; 25:319-331. [PMID: 28344485 PMCID: PMC5357111 DOI: 10.1016/j.jsps.2016.06.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 06/26/2016] [Indexed: 12/13/2022] Open
Abstract
Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.
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Key Words
- ALB, serum albumin
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Ac.E, ethyl acetate extract group
- Antioxidant
- Aq.E, aqueous extract group
- Aq.E + CCl4, aqueous extract-CCl4 group
- BACT, β-actin
- BB, total bilirubin
- CAT, catalase
- CCl3OO•, trichloromethylperoxy radical
- CCl4, carbon tetrachloride
- CCl4-induced damage
- CDNB, 1-chloro-2,4-dinitrobenzene
- CK, creatine kinase
- COX-2, cyclooxygenase
- CREA, creatinine
- DMPO, 5,5-dimethyl-1-pyrrolin-N-oxide
- EDTA, ethylenediaminetetraacetic acid disodium salt
- G6PDH, glucose-6-phosphate dehydrogenase
- GAPDH, glyceraldehyde-3 phosphate dehydrogenase
- GPx, glutathione peroxidase
- GR, glutathione reductase
- GSH, reduced form of glutathione
- GSSG, oxidized form of glutathione
- GST, glutathione-S-transferase
- H2O2, hydrogen peroxide
- HO-1, heme oxygenase-1
- He.E, hexane extract group
- He.E + CCl4, hexane extract-CCl4 group
- Hepatoprotective effects
- MDA, malondialdehyde
- Me.E, methanol extract group
- Me.E + CCl4, methanol extract-CCl4 group
- NADPH, nicotinamide adenine dinucleotide phosphate
- NBT, nitro blue tetrazolium
- NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells
- Neuroprotective effects
- Nrf2, nuclear factor erythroid-derived 2-like 2
- O.O, olive oil group
- Oxidative stress
- PPARγ, peroxisome proliferator-activated receptor gamma
- RNA, ribonucleic acid
- ROS, reactive oxygen species
- SOD, superoxide dismutase
- SOD1, superoxide dismutase-1
- SOD2, superoxide dismutase-1
- TNF-α, tumor necrosis factor
- Tilia americana var. mexicana
- UK, United Kingdom
- USA, United States of America
- Var., variant
- [Formula: see text], trichloromethyl
- bp, base pair
- i.p., intraperitoneal administration
- iNOS, inducible nitric oxide synthase
- oxo8-dG, 8-hydroxy-2′-deoxyguanosine
- γ-GLOB, γ-globulin
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Affiliation(s)
| | | | | | - Eithan Núñez-Ramírez
- Military School of Graduate of Health, Multidisciplinary Research Laboratory, SEDENA, 11270 D.F. Mexico, Mexico
| | - Esaú Floriano-Sánchez
- Military School of Graduate of Health, Multidisciplinary Research Laboratory, SEDENA, 11270 D.F. Mexico, Mexico
| | - María Eva González-Trujano
- Laboratory of Neuropharmacology of Natural Products, National Institute of Psychiatry Ramon de la Fuente Muñiz, 14370 D.F. Mexico, Mexico
| | - Berenice Fernández-Rojas
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, 04150 D.F. Mexico, Mexico
| | - José Pedraza-Chaverrí
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, 04150 D.F. Mexico, Mexico
| | | | | | - Aristides III Sampieri
- Department of Comparative Biology, Faculty of Sciences, National Autonomous University of Mexico, 04150 D.F. Mexico, Mexico
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Corrêa-Ferreira ML, Verdan MH, Dos Reis Lívero FA, Galuppo LF, Telles JEQ, Alves Stefanello MÉ, Acco A, Petkowicz CLDO. Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2017; 24:68-76. [PMID: 28160864 DOI: 10.1016/j.phymed.2016.11.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 11/04/2016] [Accepted: 11/22/2016] [Indexed: 06/06/2023]
Abstract
BACKGROUND Infusions of aerial parts of Artemisia vulgaris L. (Asteraceae) are used in herbal medicine to treat several disorders, including hepatosis. PURPOSE Evaluation of in vivo hepatoprotective effects of A. vulgaris infusion (VI) and inulin (VPI; i.e., the major polysaccharide of VI). STUDY DESIGN The hepatoprotective effect of A. vulgaris extracts on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism involved in this protection were investigated in mice. METHODS A. vulgaris infusion (VI) was prepared according to folk medicine using the aerial parts of the plant. Carbohydrate, protein, and total phenolic content was determined in VI, and its phenolic profile was determined by high-performance liquid chromatography (HPLC). Male Swiss mice were orally pretreated for 7 days with VI or VPI (once per day). On days 6 and 7 of treatment, the mice were intraperitoneally challenged with CCl4. Liver and blood were collected and markers of hepatic damage in plasma and oxidative stress in the liver were analyzed. Hepatic histology and inflammatory parameters were also studied in the liver. The scavenging activity of VI and VPI were evaluated in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS VI contained 40% carbohydrates, 2.9% proteins and 9.8% phenolic compounds. The HPLC fingerprint analysis of VI revealed chlorogenic, caffeic and dicaffeoylquinic acids as major low-molar-mass constituents. Oral pretreatment with VI and VPI significantly attenuated CCl4-induced liver damage, reduced the activity of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in plasma, and prevented reactive oxygen species accumulation and lipid peroxidation in the liver. Comparisons with the CCl4-treated group showed that VI and VPI completely prevented necrosis, increased the levels of reduced glutathione (GSH), and reduced tumor necrosis factor alpha (TNF-α) level in the liver. VI and VPI also exhibited high radical scavenging activity in vitro. CONCLUSION VI and VPI had remarkable hepatoprotective effects in vivo, which were likely attributable to antioxidant and immunomodulatory properties. The present findings support the traditional use of A. vulgaris infusion for the treatment of hepatic disorders.
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Affiliation(s)
| | - Maria Helena Verdan
- Department of Chemistry, Federal University of Parana, Curitiba, Parana, Brazil
| | | | | | | | | | - Alexandra Acco
- Department of Pharmacology, Federal University of Parana, Curitiba, Parana, Brazil
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Anti-fibrotic and anti-inflammatory effects of parboiled germinated brown rice ( Oryza sativa ‘KDML 105’) in rats with induced liver fibrosis. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.08.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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MicroRNA Expression Profiling in CCl₄-Induced Liver Fibrosis of Mus musculus. Int J Mol Sci 2016; 17:ijms17060961. [PMID: 27322257 PMCID: PMC4926493 DOI: 10.3390/ijms17060961] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/12/2016] [Accepted: 06/13/2016] [Indexed: 02/06/2023] Open
Abstract
Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs), small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl4) and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO) and in-depth pathway enrichment analysis. Herein, we found that four miRNAs were upregulated and four miRNAs were downregulated more than two-fold in CCl4-treated livers compared to a control liver. Eight miRNAs were predicted to target a total of 4079 genes. GO analysis revealed that those target genes were located in various cellular compartments, including cytoplasm, nucleolus and cell surface, and they were involved in protein-protein or protein-DNA bindings, which influence the signal transductions and gene transcription. Furthermore, pathway enrichment analysis demonstrated that the 72 subspecialized signaling pathways were associated with CCl4-induced liver fibrosis and were mostly classified into metabolic function-related pathways. These results suggest that CCl4 induces liver fibrosis by disrupting the metabolic pathways. In conclusion, we presented several miRNAs and their biological processes that might be important in the progression of liver fibrosis; these findings help increase the understanding of liver fibrogenesis and provide novel ideas for further studies of the role of miRNAs in liver fibrosis.
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Wunjuntuk K, Kettawan A, Charoenkiatkul S, Rungruang T. Parboiled Germinated Brown Rice Protects Against CCl4-Induced Oxidative Stress and Liver Injury in Rats. J Med Food 2016; 19:15-23. [DOI: 10.1089/jmf.2015.3460] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Kansuda Wunjuntuk
- Food Chemistry Division, Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand
| | - Aikkarach Kettawan
- Food Chemistry Division, Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand
| | - Somsri Charoenkiatkul
- Food Chemistry Division, Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand
| | - Thanaporn Rungruang
- Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Abdel-Moneim AM, Al-Kahtani MA, El-Kersh MA, Al-Omair MA. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage. PLoS One 2015; 10:e0144509. [PMID: 26659465 PMCID: PMC4676695 DOI: 10.1371/journal.pone.0144509] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 11/19/2015] [Indexed: 11/18/2022] Open
Abstract
The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis.
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Affiliation(s)
- Ashraf M. Abdel-Moneim
- Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Hassa, Saudi Arabia
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
- * E-mail:
| | - Mohammed A. Al-Kahtani
- Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Hassa, Saudi Arabia
| | - Mohamed A. El-Kersh
- Department of Chemistry, Faculty of Science, King Faisal University, Al-Hassa, Saudi Arabia
- Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Mohammed A. Al-Omair
- Department of Chemistry, Faculty of Science, King Faisal University, Al-Hassa, Saudi Arabia
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Na JY, Song K, Kim S, Kwon J. Hepatoprotective effect of phosphatidylcholine against carbon tetrachloride liver damage in mice. Biochem Biophys Res Commun 2015; 460:308-13. [DOI: 10.1016/j.bbrc.2015.03.031] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 03/06/2015] [Indexed: 10/23/2022]
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Abdou RH, Saleh SY, Khalil WF. Toxicological and biochemical studies on Schinus terebinthifolius concerning its curative and hepatoprotective effects against carbon tetrachloride-induced liver injury. Pharmacogn Mag 2015; 11:S93-S101. [PMID: 26109780 PMCID: PMC4461974 DOI: 10.4103/0973-1296.157705] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 09/12/2014] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recently, many efforts have been made to discover new products of natural origin which can limit the xenobiotic-induced hepatic injury. Carbon tetrachloride (CCl4) is a highly toxic chemical that is widely used to study hepatotoxicity in animal models. OBJECTIVE The present study was conducted to investigate the curative and protective effects of Schinus terbenthifolius ethanolic extract against CCl4 -induced acute hepatotoxicity in rats. MATERIALS AND METHODS S. terbenthifolius extract was orally administered in a dose of 350 mg dried extract/kg b.wt. before and after intoxication with CCl4 for curative and protective experiments, respectively. A group of hepatotoxicity indicative enzymes, oxidant-antioxidant capacity, DNA oxidation, and apoptosis markers were measured. RESULTS CCl4 increased liver enzyme leakage, oxidative stress, hepatic apoptosis, DNA oxidation, and inflammatory markers. Administration of S. terebinthifolius, either before or after CCl4 intoxication, significantly decreased elevated serum liver enzymes and reinstated the antioxidant capacity. Interestingly, S. terebinthifolius extract inhibited hepatocyte apoptosis as revealed by approximately 20 times down-regulation in caspase-3 expression when compared to CCl4 untreated group. On the other hand, there was neither protective nor curative effect of S. terebinthifolius against DNA damage caused by CCl4. CONCLUSION The present study suggests that S. terebinthifolius extract could be a substantially promising hepatoprotective agent against CCl4 toxic effects and may be against other hepatotoxic chemical or drugs.
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Affiliation(s)
- Rania H. Abdou
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Suez Canal, Ismailia 41522, Egypt
| | - Sherif Y. Saleh
- Department of Biochemistry, Faculty of Veterinary Medicine, University of Suez Canal, Ismailia 41522, Egypt
| | - Waleed F. Khalil
- Department of Pharmacology, Faculty of Veterinary Medicine, University of Suez Canal, Ismailia 41522, Egypt
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Lee IC, Kim SH, Baek HS, Moon C, Kim SH, Kim YB, Yun WK, Kim HC, Kim JC. Protective effects of diallyl disulfide on carbon tetrachloride-induced hepatotoxicity through activation of Nrf2. ENVIRONMENTAL TOXICOLOGY 2015; 30:538-548. [PMID: 24293383 DOI: 10.1002/tox.21930] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 11/11/2013] [Accepted: 11/20/2013] [Indexed: 06/02/2023]
Abstract
This study was conducted to investigate the potential effects of diallyl disulfide (DADS) on carbon tetrachloride (CCl4 )-induced acute hepatotoxicity and to determine the molecular mechanisms of protection offered by DADS in rats. DADS was administered orally at 50 and 100 mg/kg/day once daily for 5 consecutive days prior to CCl4 administration. The single oral dose of CCl4 (2 mL/kg) caused a significant elevation in serum aspartate and alanine aminotransferase activities, which decreased upon pretreatment with DADS. Histopathological examinations showed extensive liver injury, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, and congestion, which were reversed following pretreatment with DADS. The effects of DADS on cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl4 bioactivation, were also investigated. DADS pretreatment resulted in a significant decrease in CYP2E1 protein levels in dose-dependent manner. In addition, CCl4 caused a decrease in protein level of cytoplasmic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2 concurrent with downregulation of detoxifying phase II enzymes and a decrease in antioxidant enzyme activities. In contrast, DADS prevented the depletion of cytoplasmic Nrf2 and enhanced nuclear translocation of Nrf2, which, in turn, upregulated antioxidant and/or phase II enzymes. These results indicate that the protective effects of DADS against CCl4 -induced hepatotoxicity possibly involve mechanisms related to its ability to induce antioxidant or detoxifying enzymes by activating Nrf2 and block metabolic activation of CCl4 by suppressing CYP2E1.
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Affiliation(s)
- In-Chul Lee
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757, Republic of Korea
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Singh D, Arya PV, Sharma A, Dobhal MP, Gupta RS. Modulatory potential of α-amyrin against hepatic oxidative stress through antioxidant status in Wistar albino rats. JOURNAL OF ETHNOPHARMACOLOGY 2015; 161:186-193. [PMID: 25542388 DOI: 10.1016/j.jep.2014.12.025] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Revised: 12/08/2014] [Accepted: 12/16/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE α-Amyrin (a pentacyclic triterpene widely distributed in nature and isolated from a variety of plant sources and pharmacologically shown a wide spectrum of activity including anti-inflammatory, anti-ulcer, anti-hyperlipidemic, anti-tumor, and hepatoprotective actions) explored as hepatomodulator from the ethanol extract of the stem bark of Alstonia scholaris Linn. against CCl4-induced hepatic oxidative stress through antioxidant status in wistar albino rats. MATERIALS AND METHODS Experimental rats, hepato-oxidatively stressed by CCl4 (0.2 ml/kg b wt/twice a week, intra-peritoneally), were concurrently received α-amyrin (20mg/kg body weight/day, orally) for 30 consecutive days. Hepatomodulatory potential was assessed by using the serum- markers like γ-glutamyl transpeptidase (GGT), aspartate and alanine transaminases (AST, ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), and total bilirubin, total protein, glutathione reduced (GSH), ceruloplasmin, β-carotene, vitamin C and vitamin E in serum concomitantly with the hepatic-antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST), and 5´-nucleotidase, acid ribonuclease, glucose-6-phosphatase, succinic dehydrogenase and cytochrome-P-450 in liver tissue whereas lipid peroxidation (LPO) was estimated in both serum and liver contents. RESULTS The assessment of all biochemical parameters registered a significant (P<0.001) hepatic oxidative stress in CCl4 treated rats, which was considerably recovered near to almost normal level in rats co-administered with α-amyrin at the dose level of 20mg/kg body weight/day for 30 consecutive days. The histoarchitectural examination of liver sections from treated groups further corroborated the hepatomodulatory potential of α-amyrin and compared with standard drug-silymarin. CONCLUSIONS These findings indicate that the modulatory potential of α-amyrin against hepatic oxidative stress possibly involve mechanism related to its ability to block the P-450 mediated CCl4 bioactivation through selective inhibitors of ROS (reactive oxygen species) as antioxidants brought about significant inhibition of the formation of LPO suggesting possible involvement of O2(●-), HO2, HO2(●-), H2O2 and •OH. Therefore this study suggests that the use of α-amyrin as a hepatomodulatory potent to feasibility for a promising liver curative drug.
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Affiliation(s)
- Dharmendra Singh
- Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur 302 055, India; Department of Zoology, Dyal Singh College, University of Delhi, Lodhi Road, New Delhi 110 003, India
| | - P V Arya
- Department of Zoology, Dyal Singh College, University of Delhi, Lodhi Road, New Delhi 110 003, India
| | - Ashutosh Sharma
- Department of Chemistry, University of Rajasthan, Jaipur 302 055, India
| | - M P Dobhal
- Department of Chemistry, University of Rajasthan, Jaipur 302 055, India
| | - R S Gupta
- Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur 302 055, India.
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Esmaeili MA, Alilou M. Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats. Clin Exp Pharmacol Physiol 2015; 41:416-22. [PMID: 24684352 DOI: 10.1111/1440-1681.12230] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Revised: 03/02/2014] [Accepted: 03/16/2014] [Indexed: 12/11/2022]
Abstract
The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl4 )-induced liver injury in rats and the mechanism underlying its effects were investigated. Forty rats were divided into five groups. Rats in Groups I and II served as the normal and injured liver groups, respectively; Group III rats were treated with the standard drug silymarin as a positive control; and rats in Groups IV and V (naringenin-treated groups) were administrated 50 mg/kg, p.o., naringenin for 7 days. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. Naringenin inhibited lipid peroxidation and reduced serum levels of hepatic enzymes induced by CCl4 . In addition, naringenin increased the liver content of reduced glutathione and the activity of anti-oxidant enzymes in rats treated with CCl4 . Naringenin attenuated liver inflammation by downregulating CCl4 -induced activation of tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) at both the protein and mRNA levels. Naringenin treatment significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers. In rats treated with CCl4 alone, decreases were seen in nuclear Nrf2 expression and in the mRNA levels of its target genes (e.g. HO-1, NQO1 and glutathione S-transferase alpha 3 (GST-a3)). Together, the results suggest that naringenin can protect the liver against oxidative stress, presumably by activating the nuclear translocation of Nrf2 as well as attenuating the TNF-α pathway to elicit an anti-inflammatory response in liver tissue.
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Affiliation(s)
- Mohammad Ali Esmaeili
- Department of Biology, Medicinal Plants and Drug Research Institute, Shahid Beheshti University, Tehran, Iran
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Meng Q, Chen X, Wang C, Liu Q, Sun H, Sun P, Huo X, Liu Z, Liu K. Protective effects of alisol B 23-acetate from edible botanical Rhizoma alismatis against carbon tetrachloride-induced hepatotoxicity in mice. Food Funct 2015; 6:1241-50. [DOI: 10.1039/c5fo00082c] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Alisol B 23-acetate protects against CCl4-induced hepatotoxicity via FXR and STAT3-mediated gene regulation in mice.
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Affiliation(s)
- Qiang Meng
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Xinli Chen
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Changyuan Wang
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Qi Liu
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Huijun Sun
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Pengyuan Sun
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Xiaokui Huo
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Zhihao Liu
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
| | - Kexin Liu
- Department of Clinical Pharmacology
- College of Pharmacy
- Dalian Medical University
- China
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mPGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2. J Hepatol 2014; 61:1328-1336. [PMID: 25076362 PMCID: PMC4445962 DOI: 10.1016/j.jhep.2014.07.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 06/27/2014] [Accepted: 07/08/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Microsomal prostaglandin E synthase-2 (mPGES-2) deletion does not influence in vivo PGE2 production and the function of this enzyme remains elusive. The present study was undertaken to investigate the role of mPGES-2 in streptozotocin (STZ)-induced type-1 diabetes and organ injuries. METHODS mPGES-2 wild type (WT) and knockout (KO) mice were treated by a single intraperitoneal injection of STZ at the dose of 120 mg/kg to induce type-1 diabetes. Subsequently, glycemic status and organ injuries were evaluated. RESULTS Following 4 days of STZ administration, mPGES-2 KO mice exhibited severe lethality in contrast to the normal phenotype observed in WT control mice. In a separate experiment, the analysis was performed at day 3 of the STZ treatment in order to avoid lethality. Blood glucose levels were similar between STZ-treated KO and WT mice. However, the livers of KO mice were yellowish with severe global hepatic steatosis, in parallel with markedly elevated liver enzymes and remarkable stomach expansion. However, the morphology of the other organs was largely normal. The STZ-treated KO mice displayed extensive hepatocyte apoptosis compared with WT mice in parallel with markedly enhanced inflammation and oxidative stress. More interestingly, a liver-specific 50% upregulation of GLUT2 was found in the KO mice accompanied with a markedly enhanced STZ accumulation and this induction of GLUT2 was likely to be associated with the insulin/SREBP-1c pathway. Primary cultured hepatocytes of KO mice exhibited an increased sensitivity to STZ-induced injury and higher cellular STZ content, which was markedly blunted by the selective GLUT2 inhibitor phloretin. CONCLUSIONS mPGES-2 deletion enhanced STZ-induced liver toxicity possibly via GLUT2-mediated STZ uptake, independently of diabetes mellitus.
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Chatterjee N, Das S, Bose D, Banerjee S, Jha T, Saha KD. Leishmanial lipid affords protection against oxidative stress induced hepatic injury by regulating inflammatory mediators and confining apoptosis progress. Toxicol Lett 2014; 232:499-512. [PMID: 25445725 DOI: 10.1016/j.toxlet.2014.11.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 11/15/2014] [Accepted: 11/21/2014] [Indexed: 02/07/2023]
Abstract
Persistence of liver injury alters the internal milieu, promotes deregulation of inflammatory factors, and leads to dysplastic lesions like fibrosis, cirrhosis to hepatocellular carcinoma. Our previous study revealed that leishmanial lipid (pLLD) exerts potential anti-inflammatory activity in sepsis associated hepatic injury. We now show that pLLD gives protection against chemical induced hepatotoxicity in murine system. The beneficial effect of treatment with pLLD on such hepatic injury in mice was analyzed using different assays including ELISA, FACS, western blot and immunohistochemical analysis. pLLD significantly suppressed serum enzymes and rectified the histopathological alteration to induce the antioxidant level in CCl4 intoxicated liver. Levels of several growth factors including TGF-β, HGF, and EGF were significantly improved in serum and hepatic tissue with consequent reduction of caspase activities and expressions of Bad, Bax, p53, and NF-κBp65. Moreover, pLLD modulated inflammatory responses by decreasing the production of several cytokines and chemokines, thus preventing the infiltration of immune cells to the damaged area. It accelerated the repair process in liver damage with modulation of signalling cascade via alteration of apoptotic factors. Our experimental approaches suggest that pLLD effectively prevents liver injury mainly through down regulation of oxidative stress and inflammatory response towards anti-apoptotic changes.
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Affiliation(s)
- Nabanita Chatterjee
- Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Subhadip Das
- Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Dipayan Bose
- Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Somenath Banerjee
- Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Tarun Jha
- Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P. O. Box 17020, Jadavpur University, Kolkata 700032, India
| | - Krishna Das Saha
- Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India.
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Chen X, Meng Q, Wang C, Liu Q, Sun H, Huo X, Sun P, Yang X, Peng J, Liu K. Protective Effects of Calycosin Against CCl4-Induced Liver Injury with Activation of FXR and STAT3 in Mice. Pharm Res 2014; 32:538-48. [DOI: 10.1007/s11095-014-1483-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 08/15/2014] [Indexed: 12/18/2022]
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Thirunavukkarasu P, Asha S, Ramanathan T, Balasubramanian T, Shanmogapriya R, Renugadevi G. In Vitro Hepatoprotective Activity of Isolated Fractions of Cressa Cretica. Pharm Chem J 2014. [DOI: 10.1007/s11094-014-1061-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Alavian SM, Banihabib N, Es. Haghi M, Panahi F. Protective Effect of Cornus mas Fruits Extract on Serum Biomarkers in CCl4-Induced Hepatotoxicity in Male Rats. HEPATITIS MONTHLY 2014; 14:e10330. [PMID: 24829584 PMCID: PMC4006099 DOI: 10.5812/hepatmon.10330] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Revised: 10/25/2013] [Accepted: 02/11/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nowadays attention to use herbs such as cornelian cherry (Cornus mas) is increasing, which contains high levels of antioxidants and anthocyanins. Cornus mas fruits have been used for gastrointestinal and excretory disorders for many years in traditional medicine, also may improve liver and kidney functions, and have protective effects such as anti-allergic, antidiabetic, antibacterial, antimicrobial, antihistamine and antimalarial properties. OBJECTIVES The aim of this study was to investigate protective effects of Cornus mas fruits extract on serum biomarkers in CCl4-induced hepatotoxicity in male rats. MATERIALS AND METHODS Hepatotoxicity was induced by administration of carbon tetrachloride (1 mL/kg i.p.) in 1:1 dilution with olive oil. To evaluate the effect of Cornus mas fruits extract on disease progression, serum marker enzymes, serum total protein and albumin and liver lipid peroxidation were determined in CCl4-induced hepatotoxicity. RESULTS Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P < 0.05) hepatoprotection by decreasing elevated serum level of enzymes, total serum protein, albumin and liver lipid peroxidation content. CONCLUSIONS Cornus mas fruit extract effect may be due to including some antioxidant components, which caused membrane stabilizing and normalization of fluctuated biochemical profiles induced by CCl4 exposure. Our results validated the traditional use of Cornus mas in the treatment of liver disorders.
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Affiliation(s)
| | - Nafiseh Banihabib
- Liver and Gastrointestinal Diseases Research Center, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IR Iran
| | - Masoud Es. Haghi
- Baqiyatallah Research Center for Gastroenterology and Liver Disease (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Drug Applied Research Center, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IR Iran
- Corresponding Author: Masoud Es. Haghi, Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. Tel: +98-9148909189, Fax: +98-4113319716, E-mail:
| | - Farid Panahi
- Coordination Center, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IR Iran
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Sadek KM, Saleh EA. Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats. Hum Exp Toxicol 2014; 33:1277-83. [DOI: 10.1177/0960327114527629] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. Aim: The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. Methods: The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. Results: The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase ( p < 0.05) in total protein, globulin, immunoglobulin M (IgM) and IgG levels, and total antioxidant capacity. In contrast, significant decrease ( p < 0.05) in blood glucose, total cholesterol, low-density lipoprotein-cholesterol, alanine aminotransferase, C-reactive protein, and malondialdehyde levels were observed. Compared with CCl4-intoxicated rats, significant differences in the albumin, triacylglycerol, high-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, cardiovascular risk factor, calcium and magnesium levels were not detected. Conclusions: The results of the present study showed that fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said “Keep the fast, keep your health”.
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Affiliation(s)
- KM Sadek
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhur University, Egypt
| | - EA Saleh
- Department of Food Hygiene, Faculty of Veterinary Medicine, Damanhur University, Egypt
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YE SUNYI, ZHANG CHENXI, ZHOU JIE, CHENG JUN, LV ZHEN, ZHOU LIN, XIE HAIYANG, WU JIAN, ZHENG SHUSEN. Human heat shock protein 27 exacerbates ischemia reperfusion injury in rats by reducing the number of T regulatory cells. Mol Med Rep 2014; 9:1998-2002. [DOI: 10.3892/mmr.2014.2032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Accepted: 02/18/2014] [Indexed: 11/06/2022] Open
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Hepatoprotective effects of fermented field water-dropwort (Oenanthe javanica) extract and its major constituents. Food Chem Toxicol 2014; 67:154-60. [PMID: 24582681 DOI: 10.1016/j.fct.2014.02.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Revised: 11/08/2013] [Accepted: 02/07/2014] [Indexed: 11/22/2022]
Abstract
Dropwort (Oenanthe javanica) has been used for many years for the treatment of inflammatory conditions, including hepatitis. We investigated the protective effects of fermented field water-dropwort extract (FDE) on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in HepG2 cells and carbon tetrachloride (CCl4)-induced liver damage in rats. Pretreatment with FDE prior to the t-BHP treatment of HepG2 cells inhibited cell death and lactate dehydrogenase (LDH) leakage in a dose-dependent manner. In addition FDE significantly prevented the increase of hepatic enzyme markers (ALT, AST) in vivo. Moreover, FDE administration for 7 days significantly affected CYP2E1, CYP4A2, and PPARγ gene expressions. CYP2E1 and CYP4A2 gene expression in the liver, increased 2 and 22-fold by CCl4 administration, respectively, was attenuated to normal levels by pretreatment with FDE. PPARγ gene expression, completely blocked by CCl4 treatment, was increased by FDE pretreatment compared to normal control group. Histopathological examination of the livers also revealed that FDE reduced the incidence of liver lesions. Caffeic acid and chlorogenic acid were identified as major constituents of FDE. These results demonstrate the protective effects of FDE against hepatocytotoxicity induced by CCl4 and t-BHP in rats and HepG2 cells, thus indicating the potential of FDE as a therapeutic for acute liver diseases.
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Effect of Platelet-Rich Plasma on CCl4-Induced Chronic Liver Injury in Male Rats. Int J Hepatol 2014; 2014:932930. [PMID: 24707405 PMCID: PMC3953414 DOI: 10.1155/2014/932930] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 01/02/2014] [Indexed: 11/30/2022] Open
Abstract
Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1 mL/kg, i.p. 1 : 1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5 mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP.
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Mihailović V, Katanić J, Mišić D, Stanković V, Mihailović M, Uskoković A, Arambašić J, Solujić S, Mladenović M, Stanković N. Hepatoprotective effects of secoiridoid-rich extracts from Gentiana cruciata L. against carbon tetrachloride induced liver damage in rats. Food Funct 2014; 5:1795-803. [DOI: 10.1039/c4fo00088a] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The objective of this work was to investigate the effects of the methanol extracts of Gentiana cruciata L. dilate against carbon tetrachloride-induced liver injury in rats.
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Affiliation(s)
- Vladimir Mihailović
- Department of Chemistry
- Faculty of Science
- University of Kragujevac
- 34000 Kragujevac, Serbia
| | - Jelena Katanić
- Department of Chemistry
- Faculty of Science
- University of Kragujevac
- 34000 Kragujevac, Serbia
| | - Danijela Mišić
- Institute for Biological Research “Siniša Stanković”
- University of Belgrade
- 11060 Belgrade, Serbia
| | - Vesna Stanković
- Institute of Pathology
- Faculty of Medicine
- University of Kragujevac
- Serbia
| | - Mirjana Mihailović
- Institute for Biological Research “Siniša Stanković”
- University of Belgrade
- 11060 Belgrade, Serbia
| | - Aleksandra Uskoković
- Institute for Biological Research “Siniša Stanković”
- University of Belgrade
- 11060 Belgrade, Serbia
| | - Jelena Arambašić
- Institute for Biological Research “Siniša Stanković”
- University of Belgrade
- 11060 Belgrade, Serbia
| | - Slavica Solujić
- Department of Chemistry
- Faculty of Science
- University of Kragujevac
- 34000 Kragujevac, Serbia
| | - Milan Mladenović
- Department of Chemistry
- Faculty of Science
- University of Kragujevac
- 34000 Kragujevac, Serbia
| | - Nevena Stanković
- Department of Chemistry
- Faculty of Science
- University of Kragujevac
- 34000 Kragujevac, Serbia
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Lee IC, Kim SH, Baek HS, Moon C, Kang SS, Kim SH, Kim YB, Shin IS, Kim JC. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food Chem Toxicol 2013; 63:174-85. [PMID: 24246655 DOI: 10.1016/j.fct.2013.11.006] [Citation(s) in RCA: 101] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 10/24/2013] [Accepted: 11/06/2013] [Indexed: 12/31/2022]
Abstract
This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-κB) and phosphorylation of I kappaB alpha (IκBα) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-κB translocation and IκBα phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-κB activation.
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Affiliation(s)
- In-Chul Lee
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea
| | - Sung-Hwan Kim
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea
| | - Hyung-Seon Baek
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea
| | - Changjong Moon
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea
| | - Seong-Soo Kang
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea
| | - Sung-Ho Kim
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea
| | - Yun-Bae Kim
- College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea
| | - In-Sik Shin
- Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
| | - Jong-Choon Kim
- College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
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Shah NA, Khan MR, Ahmad B, Noureen F, Rashid U, Khan RA. Investigation on flavonoid composition and anti free radical potential of Sida cordata. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 13:276. [PMID: 24148097 PMCID: PMC3874743 DOI: 10.1186/1472-6882-13-276] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Accepted: 10/10/2013] [Indexed: 01/06/2023]
Abstract
BACKGROUND Sida cordata, a member of Family Malvaceae is used in folk medicine for various ailments including liver diseases. In this study we investigated, its flavonoid constituents, in vitro antioxidant potential against different free radicals and hepatoprotection against carbon tetrachloride (CCl4)-induced liver damage in rat. METHODS Dried powder of S. cordata whole plant was extracted with methanol and the resultant (SCME) obtained was fractionated with escalating polarity to obtain n-hexane fraction (SCHE), ethyl acetate fraction (SCEE), n-butanol fraction (SCBE) and the remaining soluble portion as aqueous fraction (SCAE). Diverse in vitro antioxidants assays such as DPPH, H2O2, •OH, ABTS, β-carotene bleaching assay, superoxide radical, lipid peroxidation, reducing power, and total antioxidant capacity were studied to assess scavenging potential of methanol extract and its derived fractions. On account of marked scavenging activity SCEE was selected to investigate the hepatoprotective potential against CCl4 induced toxicity in Sprague-Dawley male rats by assessing the level of serum markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, lactate dehydrogenase, bilirubin, and γ-glutamyltransferase) and of liver antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione-S-transfers (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) and lipid peroxidation (TBARS). Histology of the liver was performed to study alteration in histoarchitecture. Existence of active flavonoids was established by thin layer chromatographic studies. RESULTS Considerable amount of flavonoid and phenolic contents were recorded in the methanol extract and its derived fractions. Although the extract and all its derived fractions exhibited good antioxidant activities however, the most distinguished scavenging potential was observed for SCEE. Treatment of SCEE decreased the elevated level of serum marker enzymes induced with CCl4 administration whereas increased the activity of hepatic antioxidant enzymes (CAT, SOD, POD, GST, GSR and GSH-Px). Hepatic concentration of GSH was increased while lipid peroxidation was decreased with SCEE administration in CCl4 intoxicated rats. Presence of apigenin with some unknown compounds was observed in SCEE by using thin layer chromatography. CONCLUSIONS These results revealed the presence of some bioactive compound in the ethyl acetate fraction, confirming the utility of S. cordata against liver diseases in folk medicine.
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Affiliation(s)
- Naseer Ali Shah
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Muhammad Rashid Khan
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Bushra Ahmad
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Farah Noureen
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Umbreen Rashid
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Rahmat Ali Khan
- Deparment of Biotechnology, Faculty of Biological Sciences, University of Science and Technology Bannu, Khyber Pakhtunkhwa, Pakistan
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Quan J, Li T, Zhao W, Xu H, Qiu D, Yin X. Hepatoprotective effect of polysaccharides from Boschniakia rossica on carbon tetrachloride-induced toxicity in mice. J Clin Biochem Nutr 2013; 52:244-52. [PMID: 23704815 PMCID: PMC3652299 DOI: 10.3164/jcbn.12-96] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2012] [Accepted: 11/15/2012] [Indexed: 11/29/2022] Open
Abstract
The purpose of this study was to investigate the protective effect of polysaccharides from Boschniakia rossica against hepatotoxicity induced by carbon tetrachloride (CCl4). Boschniakia rossica polysaccharides was administered intragastrically once daily for 7 days. One hour after the final treatment, mice were treated intraperitoneally with 80 mg/kg of CCl4. CCl4-induced hepatotoxicity was manifested by increased levels of serum marker enzymes and hepatic lipid peroxidation, and by decreased potential of hepatic antioxidative defense system. CCl4 challenge also resulted in elevated serum tumor necrosis factor-α and hepatic nitric oxide level, and up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 proteins of liver tissue. Pretreatment of mice with Boschniakia rossica polysaccharides reversed these altered parameters of mice with liver injury induced by CCl4. Furthermore, caspase-3 cleavage and activities, and DNA fragmentation of liver in mice treated with Boschniakia rossica polysaccharides were decreased than mice treated with CCl4 alone. Hepatoprotective effect of Boschniakia rossica polysaccharides was further demonstrated by histopathological examination of liver sections. The results indicate that Boschniakia rossica polysaccharides play a protective role in CCl4-induced acute liver injury and the hepatoprotective effect of Boschniakia rossica polysaccharides may be due to elevated antioxidative defense potentials, suppressed inflammatory responses and apoptosis of liver tissue.
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Affiliation(s)
- Jishu Quan
- Department of Biochemistry and Molecular Biology, Basic Medical College of Yanbian University, Yanji, Jilin Province 133000, China ; Department of Physiology and Pathophysiology, Medical College of Yanbian University, Yanji, Jilin Province 133000, China
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Protection against experimental salmonellosis by recombinant 49 kDa OMP of Salmonella enterica serovar Typhi: biochemical aspects. Biologia (Bratisl) 2013. [DOI: 10.2478/s11756-013-0160-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Wu S, Ma XB, Zhou CJ, Zhao JJ, Guo JQ, Xu WH. Nuclear translocation of Nrf2 in hepatocytes of mice with hepatic fibrosis. Shijie Huaren Xiaohua Zazhi 2013; 21:739-744. [DOI: 10.11569/wcjd.v21.i9.739] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the nuclear translocation of NF-E2-related factor 2 (Nrf2) in hepatocytes of mice with hepatic fibrosis.
METHODS: Mice were randomly divided into two groups: normal control group and model group. For the model group, carbon tetrachloride (CCl4) dissolved in mineral oil was injected intraperitoneally for 10 weeks, while the normal control group was injected with the same volume of mineral oil. At the end of the 10th week, specimens were collected to assess the degrees of hepatic fibrosis and inflammation by haematoxylin-eosin staining and Masson staining. Western blot was used to detect the protein expression of Nrf2 and NAD(P)H quinine oxidoreductase 1 (Nqo1) and nuclear translocation of Nrf2.
RESULTS: Compared to the normal control group, the degrees of hepatic inflammation and fibrosis in the model group were significantly increased. Western blot analysis showed that, compared to the normal control group (0.490 ± 0.088, 0.430 ± 0.057, 0.370 ± 0.022), the expression levels of Nrf2 and Nqo1 proteins, as well as nuclear translocation of Nrf2 were increased significantly in the model group (0.490 ± 0.088 vs 0.790 ± 0.045, 0.430 ± 0.057 vs 0.720 ± 0.040, 0.370 ± 0.022 vs 0.670 ± 0.044; F = 2.027, 0.772, 1.552, all P < 0.05).
CONCLUSION: In mice with hepatic fibrosis, the nuclear translocation of Nrf2 in hepatocytes is increased to up-regulate its target protein Nqo1.
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Chen S, Zou L, Li L, Wu T. The protective effect of glycyrrhetinic acid on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. PLoS One 2013; 8:e53662. [PMID: 23341968 PMCID: PMC3544925 DOI: 10.1371/journal.pone.0053662] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2012] [Accepted: 12/03/2012] [Indexed: 12/22/2022] Open
Abstract
This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl4.Then, CCl4 administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl4 exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases.
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Affiliation(s)
- Shaoru Chen
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
| | - Liyi Zou
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
| | - Li Li
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
| | - Tie Wu
- The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China
- * E-mail:
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Jin CF, Li B, Lin SM, Yadav RK, Kim HR, Chae HJ. Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts (EUCE) in the CCl 4 -Induced Acute Liver Lipid Accumulation in Rats. Int J Endocrinol 2013; 2013:751854. [PMID: 24027582 PMCID: PMC3762164 DOI: 10.1155/2013/751854] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 04/21/2013] [Accepted: 06/21/2013] [Indexed: 01/18/2023] Open
Abstract
Eucommia ulmoides Oliv. (EU) has been used for treatment of liver diseases. The protective effects of Eucommia Ulmoides Oliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4 decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4 treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4 treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4 reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.
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Affiliation(s)
- Chang-Feng Jin
- Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Jeonju 561-180, Republic of Korea
| | - Bo Li
- Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Jeonju 561-180, Republic of Korea
| | - Shun-Mei Lin
- Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Jeonju 561-180, Republic of Korea
| | - Raj-Kumar Yadav
- Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Jeonju 561-180, Republic of Korea
| | - Hyung-Ryong Kim
- Department of Dental Pharmacology and Wonkwang Biomaterial Implant Research Institute, School of Dentistry, Wonkwang University, Chonbuk, Iksan 570-749, Republic of Korea
| | - Han-Jung Chae
- Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Jeonju 561-180, Republic of Korea
- *Han-Jung Chae:
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Lee CC, Shen SR, Lai YJ, Wu SC. Rutin and quercetin, bioactive compounds from tartary buckwheat, prevent liver inflammatory injury. Food Funct 2013; 4:794-802. [DOI: 10.1039/c3fo30389f] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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