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Sun YQ, Wu Y, Li MR, Wei YY, Guo M, Zhang ZL. Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function. World J Gastroenterol 2024; 30:4660-4668. [PMID: 39575408 PMCID: PMC11572637 DOI: 10.3748/wjg.v30.i43.4660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/29/2024] [Accepted: 10/18/2024] [Indexed: 10/31/2024] Open
Abstract
We discuss the article by Koizumi et al published in the World Journal of Gastroenterology. Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease (ALD) and the mechanism of action of elafibranor (EFN), a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and peroxisome PPAR δ (PPARδ). EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis. ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis (ASH), with chronic ASH eventually leading to fibrosis, cirrhosis, and, in some cases, hepatocellular carcinoma. The pathogenesis of ALD is driven by hepatic steatosis, oxidative stress, and acetaldehyde toxicity. Alcohol consumption disrupts lipid metabolism by inactivating PPARα, exacerbating the progression of ALD. EFN primarily activates PPARα, promoting lipolysis and β-oxidation in ethanol-stimulated HepG2 cells, which significantly reduces hepatic steatosis, apoptosis, and fibrosis in an ALD mouse model. Additionally, alcohol disrupts the gut-liver axis at several interconnected levels, contributing to a proinflammatory environment in the liver. EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy, inhibiting apoptosis and inflammatory responses, and enhancing intestinal barrier function through PPARδ activation.
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Affiliation(s)
- Yu-Qi Sun
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Yang Wu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Meng-Ran Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Yu-Yao Wei
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Mei Guo
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Zi-Li Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
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Yuba T, Koyama Y, Kinishi Y, Uokawa R, Ootaki C, Shimada S, Fujino Y. Analysis of Maternal and Fetal Oxidative Stress During Delivery with Epidural Analgesia. Reprod Sci 2024; 31:2753-2762. [PMID: 38727999 PMCID: PMC11393216 DOI: 10.1007/s43032-024-01580-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 04/26/2024] [Indexed: 09/14/2024]
Abstract
Childbirth is a stressful event for mothers, and labor epidural analgesia (LEA) may reduce mental stress. Mental stressors include labor pain, fear, and anxiety, which induce oxidative stress. In this study, we focused on oxidative stress during delivery and conducted a cross-sectional analysis of maternal and fetal oxidative stress. The participants included 15 women who received LEA (LEA group) and 15 who did not (No LEA group). Participants with a gestational age of < 37 weeks, BMI of ≥ 35 kg/m2, cerebrovascular or cardiovascular complications, multiple pregnancies, gestational hypertension, gestational diabetes, chronic hypertension, thyroid disease, birth weight of < 2,500 g, emergency cesarean section, or cases in which epidural anesthesia was re-administered during delivery were excluded from the study. Maternal blood was collected on admission, and immediately after delivery, and umbilical artery blood was collected from the fetus. The oxidative stress status was assessed by measuring diacron-reactive oxygen metabolite (an index of the degree of lipid peroxide oxidation), biological antioxidant potential (an index of antioxidant capacity) and calculating the ratio of BAP/d-ROMs (an index of the oxidative stress). The results showed that maternal oxidative stress immediately after delivery was lower in the LEA group than in the No LEA group. Moreover, the fetuses experienced less oxidative stress in the LEA group than in the No LEA group. Taken together, these results suggest that LEA may reduce maternal and fetal oxidative stress associated with childbirth.
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Affiliation(s)
- Tomoo Yuba
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
- Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Yoshihisa Koyama
- Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
- Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka, 541-8567, Japan.
- Global Center for Medical Engineering and Informatics, Osaka University, Suita, 565-0871, Japan.
- Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, 565-0871, Japan.
| | - Yuki Kinishi
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Reiko Uokawa
- Department of Anesthesiology, Chibune General Hospital, Osaka, 555-0034, Japan
| | - Chiyo Ootaki
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shoichi Shimada
- Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka, 541-8567, Japan
- Global Center for Medical Engineering and Informatics, Osaka University, Suita, 565-0871, Japan
| | - Yuji Fujino
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Zhu C, Liu G, Abdullah ALB, Han M, Jiang Q, Li Y. Transcriptomic analysis following polystyrene nanoplastic stress in the Pacific white shrimp, Litopenaeus vannamei. FISH & SHELLFISH IMMUNOLOGY 2023; 143:109207. [PMID: 37923183 DOI: 10.1016/j.fsi.2023.109207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 10/28/2023] [Accepted: 10/31/2023] [Indexed: 11/07/2023]
Abstract
Plastics are widely produced for industrial and domestic applications due to their unique properties, and studies on the toxic effects of nanoplastics (NPs) on aquatic animals are essential. In this study, we investigated the transcriptomic patterns of Litopenaeus vannamei after NPs exposure. We found that the lysosome pathway was activated when after NPs exposure, with up-regulated DEGs, including glucocerebrosidase (GBA), hexosaminidase A (HEXA), sphingomyelin phosphodiesterase-1 (SMPD1), and solute carrier family 17 member 5 (SLC17A5). In addition, the PI3K-Akt signaling pathway was strongly affected by NPs, and the upstream genes of PI3K-Akt, including epidermal growth factor receptor (EGFR), integrin subunit beta 1 (ITGB1) and heat shock protein 90 (HSP90) were up-regulation. Other genes involved in lipogenesis, such as sterol regulatory element binding transcription factor 1 (SREBP-1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD-1), were down-regulated. However, the contents of triglycerides (TG) and total cholesterol (TCH) in L. vanname hepatopancreas were reduced, which indicated that the ingestion of NPs led to the disturbance of hepatic lipid metabolism. What more, NPs treatment of L. vannamei also caused oxidative stress. In addition, NPs can damage part of the tissue structure and affect the physiological function of shrimps. The results of this study provide valuable ecotoxicological data to improve the understanding of the biological fate and effects of nanoplastics in L. vannamei.
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Affiliation(s)
- Chenxi Zhu
- Freshwater Fisheries Research Institute of Jiangsu Province, 79 Chating East Street, Nanjing, 210017, China; Low-temperature Germplasm Bank of Important Economic Fish (Freshwater Fisheries Research Institute of Jiangsu Province) of Jiangsu Provincial Science and Technology Resources (Agricultural Germplasm Resources) Coordination Service Platform, Nanjing, China; Geography, School of Humanities, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia
| | - Guoxing Liu
- Freshwater Fisheries Research Institute of Jiangsu Province, 79 Chating East Street, Nanjing, 210017, China; Low-temperature Germplasm Bank of Important Economic Fish (Freshwater Fisheries Research Institute of Jiangsu Province) of Jiangsu Provincial Science and Technology Resources (Agricultural Germplasm Resources) Coordination Service Platform, Nanjing, China
| | | | - Mingming Han
- Freshwater Fisheries Research Institute of Jiangsu Province, 79 Chating East Street, Nanjing, 210017, China
| | - Qichen Jiang
- Freshwater Fisheries Research Institute of Jiangsu Province, 79 Chating East Street, Nanjing, 210017, China.
| | - Yiming Li
- Fishery Machinery and Instrument Research Institute, Chinese Academy of Fisheries Sciences, Shanghai, 200092, China.
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Abdelrahman MT, Maina EN, Elshemy HA. Clove (Syzygium aromaticum) and honey extracts significantly reduce inflammatory cytokines and liver function enzymes in experimental rats fed on carbon tetrachloride (CCl4). JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2019. [DOI: 10.1016/j.jrras.2018.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Mohamad T. Abdelrahman
- Radiobiochemistry Unit, Egyptian Atomic Energy Authority, Cairo, Egypt
- Molecular Biology and Biotechnology Dept, Pan African University, Nairobi, Kenya
| | - Esther N. Maina
- Department of Biochemistry University of Nairobi, Nairobi, Kenya
| | - Hany A. Elshemy
- Department of Biochemistry, Faculty of Agriculture, Cairo University, Cairo, Egypt
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Roy S, Chikkerur J, Roy SC, Dhali A, Kolte AP, Sridhar M, Samanta AK. Tagatose as a Potential Nutraceutical: Production, Properties, Biological Roles, and Applications. J Food Sci 2018; 83:2699-2709. [PMID: 30334250 DOI: 10.1111/1750-3841.14358] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 06/29/2018] [Accepted: 08/28/2018] [Indexed: 11/29/2022]
Abstract
Nutraceuticals are gaining importance owing to their potential applications in numerous sectors including food and feed industries. Among the emerging nutraceuticals, d-tagatose occupies a significant niche because of its low calorific value, antidiabetic property and growth promoting effects on beneficial gut bacteria. As d-tagatose is present in minute quantities in naturally occurring food substances, it is produced mainly by chemical or biological means. Recently, attempts were made for bio-production of d-tagatose using l-arabinose isomerase enzyme to overcome the challenges of chemical process of production. Applications of d-tagatose for maintaining health and wellbeing are increasing due to growing consumer awareness and apprehension against modern therapeutic agents. This review outlines the current status on d-tagatose, particularly its production, properties, biological role, applications, and the future perspectives.
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Affiliation(s)
- Sohini Roy
- Jain Univ., ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
| | - Jayaram Chikkerur
- Jain Univ., ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
| | - Sudhir Chandra Roy
- Molecular Biology Unit, ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
| | - Arindam Dhali
- Omics Lab., ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
| | - Atul Puroshtam Kolte
- Omics Lab., ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
| | - Manpal Sridhar
- BE & ES Div., ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
| | - Ashis Kumar Samanta
- Feed Additives & Nutraceuticals Lab., ICAR-NIANP, Adugodi, Hosur Road, Bengaluru - 560 030, Karnataka, India
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Hamezah HS, Durani LW, Ibrahim NF, Yanagisawa D, Kato T, Shiino A, Tanaka S, Damanhuri HA, Ngah WZW, Tooyama I. Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions. Exp Gerontol 2017; 99:69-79. [PMID: 28918364 DOI: 10.1016/j.exger.2017.09.008] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 09/02/2017] [Accepted: 09/12/2017] [Indexed: 10/18/2022]
Abstract
Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age.
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Affiliation(s)
- Hamizah Shahirah Hamezah
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
| | - Lina Wati Durani
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
| | - Nor Faeizah Ibrahim
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan; Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
| | - Daijiro Yanagisawa
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
| | - Tomoko Kato
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
| | - Akihiko Shiino
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
| | - Sachiko Tanaka
- Department of Medical Statistics, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
| | - Hanafi Ahmad Damanhuri
- Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
| | - Wan Zurinah Wan Ngah
- Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
| | - Ikuo Tooyama
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
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Sugimoto K, Takei Y. Pathogenesis of alcoholic liver disease. Hepatol Res 2017; 47:70-79. [PMID: 27138729 DOI: 10.1111/hepr.12736] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 04/26/2016] [Accepted: 04/29/2016] [Indexed: 02/06/2023]
Abstract
Alcoholic liver disease (ALD) has become one of the most critical health problems in many countries, including Japan. Liver injury in ALD ranges from steatosis and steatohepatitis to fibrosis, cirrhosis, and hepatocellular carcinoma. Many factors are thought to contribute to the development and progression of ALD, particularly insulin resistance, generation of reactive oxygen species during alcohol metabolism, adipokines from visceral adipose tissue, and endotoxin derived from the gut. Although the pathogenesis of ALD has been widely investigated, the precise mechanisms are yet to be elucidated and many questions remain. This article reviews the possible mechanisms for the development of ALD identified to date.
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Affiliation(s)
- Kazushi Sugimoto
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie, Japan
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Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging? Cent Eur J Immunol 2016; 41:116-24. [PMID: 27095931 PMCID: PMC4829813 DOI: 10.5114/ceji.2015.56973] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 07/20/2015] [Indexed: 12/21/2022] Open
Abstract
Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.
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Fatma M, Masood A, Per TS, Khan NA. Nitric Oxide Alleviates Salt Stress Inhibited Photosynthetic Performance by Interacting with Sulfur Assimilation in Mustard. FRONTIERS IN PLANT SCIENCE 2016; 7:521. [PMID: 27200007 PMCID: PMC4842777 DOI: 10.3389/fpls.2016.00521] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 04/04/2016] [Indexed: 05/19/2023]
Abstract
The role of nitric oxide (NO) and sulfur (S) on stomatal responses and photosynthetic performance was studied in mustard (Brassica juncea L.) in presence or absence of salt stress. The combined application of 100 μM NO (as sodium nitroprusside) and 200 mg S kg(-1) soil (S) more prominently influenced stomatal behavior, photosynthetic and growth performance both in the absence and presence of salt stress. The chloroplasts from salt-stressed plants had disorganized chloroplast thylakoids, but combined application of NO and S resulted in well-developed chloroplast thylakoids and properly stacked grana. The leaves from plants receiving NO plus S exhibited lower superoxide ion accumulation under salt stress than the plants receiving NO or S. These plants also exhibited increased activity of ATP-sulfurylase (ATPS), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and optimized NO generation that helped in minimizing oxidative stress. The enhanced S-assimilation of these plants receiving NO plus S resulted in increased production of cysteine (Cys) and reduced glutathione (GSH). These findings indicated that NO influenced photosynthesis under salt stress by regulating oxidative stress and its effects on S-assimilation, an antioxidant system and NO generation. The results suggest that NO improves photosynthetic performance of plants grown under salt stress more effectively when plants received S.
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Goh LPW, Chong ETJ, Chua KH, Chuah JA, Lee PC. Significant genotype difference in the CYP2E1 PstI polymorphism of indigenous groups in Sabah, Malaysia with Asian and non-Asian populations. Asian Pac J Cancer Prev 2015; 15:7377-81. [PMID: 25227845 DOI: 10.7314/apjcp.2014.15.17.7377] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations.
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Affiliation(s)
- Lucky Poh Wah Goh
- Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu, Sabah, Malaysia E-mail :
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Hazini A, Cemek M, Işıldak İ, Alpdağtaş S, Önül A, Şenel Ü, Kocaman T, Dur A, Iraz M, Uyarel H. Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction. ADVANCES IN INTERVENTIONAL CARDIOLOGY 2015; 11:298-303. [PMID: 26677379 PMCID: PMC4679797 DOI: 10.5114/pwki.2015.55600] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 02/11/2015] [Accepted: 04/20/2015] [Indexed: 12/05/2022] Open
Abstract
INTRODUCTION Acute myocardial infarction (AMI) is still one of the most common causes of death worldwide. In recent years, for diagnosis of myocardial ischemia, a new parameter, called ischemia modified albumin (IMA), which is thought to be more advantageous than common methods, has been researched. AIM In this study, systematic analysis of parameters considered to be related to myocardial ischemia has been performed, comparing between control and myocardial ischemia groups. MATERIAL AND METHODS We selected 40 patients with AMI and 25 healthy controls for this study. Ischemia modified albumin levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) antioxidant enzyme activities and non-enzymatic antioxidants such as retinol, α-tocopherol, β-carotene and ascorbic acid levels were investigated in both groups. Glutathione (GSH) and malondialdehyde (MDA) levels, which are indicators of oxidative stress, were compared between patient and control groups. RESULTS Ischemia modified albumin levels were found significantly higher in the AMI diagnosed group when compared with controls. The MDA level was elevated in the patient group, whereas the GSH level was decreased. SOD, GPx and CAT enzyme levels were decreased in the patient group, where it could be presumed that oxidative stress causes the cardiovascular diseases. CONCLUSIONS Due to the increased oxidative stress, non-enzymatic and enzymatic antioxidant capacity was affected. Systematic investigation of parameters related to myocardial infarction has been performed, and it is believed that such parameters can contribute to protection and early diagnosis of AMI and understanding the mechanism of development of the disease.
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Affiliation(s)
- Ahmet Hazini
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - Mustafa Cemek
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - İbrahim Işıldak
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - Saadet Alpdağtaş
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - Abdullah Önül
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - Ünal Şenel
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - Tuba Kocaman
- Department of Bioengineering (Biochemistry Division), Chemical and Metallurgical Engineering Faculty, Yıldız Technical University, Istanbul, Turkey
| | - Ali Dur
- Department of Emergency, Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey
| | - Mustafa Iraz
- Department of Pharmacology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Hüseyin Uyarel
- Department of Cardiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
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12
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Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism. World J Gastroenterol 2014; 20:17756-17772. [PMID: 25548474 PMCID: PMC4273126 DOI: 10.3748/wjg.v20.i47.17756] [Citation(s) in RCA: 344] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 05/22/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility.
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Borra SK, Mahendra J, Gurumurthy P, Jayamathi, Iqbal SS, Mahendra L. Effect of curcumin against oxidation of biomolecules by hydroxyl radicals. J Clin Diagn Res 2014; 8:CC01-5. [PMID: 25478334 PMCID: PMC4253152 DOI: 10.7860/jcdr/2014/8517.4967] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 07/07/2014] [Indexed: 12/24/2022]
Abstract
BACKGROUND Among various reactive oxygen species, hydroxyl radicals have the strongest chemical activity, which can damage a wide range of essential biomolecules such as lipids, proteins, and DNA. OBJECTIVE The objective of this study was to investigate the beneficial effects of curcumin on prevention of oxidative damage of biomolecules by hydroxyl radicals generated in in vitro by a Fenton like reaction. MATERIALS AND METHODS We have incubated the serum, plasma and whole blood with H2O2/Cu2+/ Ascorbic acid system for 4 hours at 37 0C and observed the oxidation of biomolecules like albumin, lipids, proteins and DNA. RESULTS Curcumin at the concentrations of 50,100 and 200 μmoles, prevented the formation of ischemia modified albumin, MDA, protein carbonyls, oxidized DNA and increased the total antioxidant levels and GSH significantly. CONCLUSION These observations suggest the hydroxyl radical scavenging potentials of curcumin and protective actions to prevent the oxidation of biomolecules by hydroxyl radicals.
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Affiliation(s)
- Sai Krishna Borra
- Research Scholar, Department of Biochemistry, Frontier Lifeline Hospital, Mogappair, Chennai, India
| | - Jaideep Mahendra
- Professor, Department of Periodontics, Meenakshi Ammal Dental College, Madhuravoyal, Chennai, India
| | - Prema Gurumurthy
- Director - Research, Meenakshi Academy of Higher Education and Research, West K.K. Nagar, Chennai, India
| | - Jayamathi
- Professor, Department of Biochemistry, Meenakshi Ammal Dental College, Madhuravoyal, Chennai, India
| | - Shabeer S Iqbal
- Research Scholar, Department of Biochemistry, Frontier Lifeline Hospital, Mogappair, Chennai, India
| | - Little Mahendra
- Associate Professor, Department of Periodontology, Raja Muthaiah Dental college and Hospital, Annamalai University, Chidambaram, India
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Hakucho A, Liu J, Liu X, Fujimiya T. Carvedilol improves ethanol-induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats. Hepatol Res 2014; 44:560-70. [PMID: 23607506 DOI: 10.1111/hepr.12143] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2012] [Revised: 04/02/2013] [Accepted: 04/17/2013] [Indexed: 12/20/2022]
Abstract
AIM Oxidative stress is a major pathway mediating ethanol hepatotoxicity and liver injury. We previously found that carvedilol, which can block the sympathetic nervous system via β1-, β2- and α1-adrenoreceptors, modifies ethanol-induced production of lipogenesis- and fibrogenesis-related mediators from hepatic stellate cells (HSC). In the present study, we assessed the effects of carvedilol on ethanol-induced liver injury, hepatic insulin resistance, and the interaction between oxidative stress and sympathetic hyperactivity in rats with alcoholic fatty liver disease (AFLD). METHODS Male Wistar rats were pair-fed for 49 days and divided into four groups: control and ethanol liquid-diet-fed rats with and without 7-day carvedilol treatment. Rats' sympathetic activity, hepatic oxidative stress, hepatic insulin resistance and liver injury were evaluated based on biochemical analysis, enzyme-linked immunosorbent assay, fluorescence immunohistochemistry, western blot and reverse transcriptase polymerase chain reaction. RESULTS Forty-nine days of ethanol consumption induced the increases in circulating noradrenaline metabolite (3-methoxy-4-hydroxyphenylglycol), hepatic noradrenaline and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, the downregulation of hepatic insulin receptor substrate-1 gene expression, and the accumulation of fatty droplets within hepatocytes with the increased hepatic triglyceride and blood alanine aminotransferase levels. All of these changes were modified by carvedilol treatment. 8-OHdG was detected in activated HSC and suppressed by carvedilol treatment based on fluorescence immunohistochemical double-staining analysis. CONCLUSION Carvedilol may modify the interaction between the oxidative stress and the sympathetic hyperactivity, and then contribute to attenuating the development of AFLD in rats. Additionally, oxidative stress may be responsible for the activation of HSC during the early stage of alcoholic liver disease.
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Affiliation(s)
- Ayako Hakucho
- Department of Legal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
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Sid B, Verrax J, Calderon PB. Role of oxidative stress in the pathogenesis of alcohol-induced liver disease. Free Radic Res 2013; 47:894-904. [PMID: 23800214 DOI: 10.3109/10715762.2013.819428] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Chronic alcohol consumption is a well-known risk factor for liver disease, which represents a major cause of morbidity and mortality worldwide. The pathological process of alcohol-induced liver disease is characterized by a broad spectrum of morphological changes ranging from steatosis with minimal injury to more advanced liver damage, including steato-hepatitis and fibrosis/cirrhosis. Experimental and clinical studies increasingly show that the oxidative damage induced by ethanol contribute in many ways to the pathogenesis of alcohol hepatotoxicity. This article describes the contribution of oxidative mechanisms to liver damage by alcohol.
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Affiliation(s)
- B Sid
- Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group (GTOX) , Brussels , Belgium
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Demiryilmaz I, Sener E, Cetin N, Altuner D, Suleyman B, Albayrak F, Akcay F, Suleyman H. Biochemically and histopathologically comparative review of thiamine's and thiamine pyrophosphate's oxidative stress effects generated with methotrexate in rat liver. Med Sci Monit 2013. [PMID: 23197226 PMCID: PMC3560789 DOI: 10.12659/msm.883591] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Background Oxidative liver injury occurring with methotrexate restricts its use in the desired dose. Therefore, whether or not thiamine and thiamine pyrophosphate, whose antioxidant activity is known, have protective effects on oxidative liver injury generated with methotrexate was comparatively researched in rats using biochemical and histopathological approaches. Material/Methods Thiamine pyrophosphate+methotrexate, thiamine+methotrexate, and methotrexate were injected intraperitoneally in rats for 7 days. After this period, all animals’ livers were excised, killing them with high-dose anesthesia, and histopathologic and biochemical investigations were made. Result Biochemical results demonstrated a significant elevation in level of oxidant parameters such as MDA and MPO, and a reduction in antioxidant parameters such as GSH and SOD in the liver tissue of the methotrexate group. Also, the quantity of 8-OHdG/dG, a DNA injury product, was higher in the methotrexate group with high oxidant levels and low antioxidant levels, and the quantity of 8-OHdG/dG was in the thiamine pyrophosphate group with low oxidant levels and high antioxidant levels. In the thiamine and control groups, the 8-OHdG/dG rate was 1.48±0.35 pmol/L (P>0.05) and 0.55±0.1 pmol/L (P<0.0001). Thiamine pyrophosphate significantly decreased blood AST, ALT and LDH, but methotrexate and thiamine did not decrease the blood levels of AST, ALT and LDH. Histopathologically, although centrilobular necrosis, apoptotic bodies and inflammation were monitored in the methotrexate group, the findings in the thiamine pyrophosphate group were almost the same as in the control group. Conclusions Thiamine pyrophosphate was found to be effective in methotrexate hepatotoxicity, but thiamine was ineffective.
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Sid B, Verrax J, Calderon PB. Role of AMPK activation in oxidative cell damage: Implications for alcohol-induced liver disease. Biochem Pharmacol 2013; 86:200-9. [PMID: 23688501 DOI: 10.1016/j.bcp.2013.05.007] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 05/03/2013] [Accepted: 05/08/2013] [Indexed: 02/08/2023]
Abstract
Chronic alcohol consumption is a well-known risk factor for liver disease. Progression of alcohol-induced liver disease (ALD) is a multifactorial process that involves a number of genetic, nutritional and environmental factors. Experimental and clinical studies increasingly show that oxidative damage induced by ethanol contributes in many ways to the pathogenesis of alcohol hepatoxicity. Oxidative stress appears to activate AMP-activated protein kinase (AMPK) signaling system, which has emerged in recent years as a kinase that controls the redox-state and mitochondrial function. This review focuses on the most recent insights concerning the activation of AMPK by reactive oxygen species (ROS), and describes recent evidences supporting the hypothesis that AMPK signaling pathways play an important role in promoting cell viability under conditions of oxidative stress, such as during alcohol exposure. We suggest that AMPK activation by ROS can promote cell survival by inducing autophagy, mitochondrial biogenesis and expression of genes involved in antioxidant defense. Hence, increased intracellular concentrations of ROS may represent a general mechanism for enhancement of AMPK-mediated cellular adaptation, including maintenance of redox homeostasis. On the other hand, AMPK inhibition in the liver by ethanol appears to play a key role in the development of steatosis induced by chronic alcohol consumption. Although more studies are needed to assess the functions of AMPK during oxidative stress, AMPK may be a possible therapeutic target in the particular case of alcohol-induced liver disease.
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Affiliation(s)
- Brice Sid
- Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group GTOX, Brussels, Belgium
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Khan MN, Siddiqui MH, Mohammad F, Naeem M. Interactive role of nitric oxide and calcium chloride in enhancing tolerance to salt stress. Nitric Oxide 2012; 27:210-8. [DOI: 10.1016/j.niox.2012.07.005] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Revised: 07/15/2012] [Accepted: 07/20/2012] [Indexed: 10/28/2022]
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Dhawan D, Sen T, Dani V. Effectiveness of Zinc in Modulating the CCl (4) - Induced Oxidative Stress in Rat Liver. Toxicol Mech Methods 2012; 16:37-40. [PMID: 20021039 DOI: 10.1080/15376520500194676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The present study was designed to evaluate the role of zinc on the enzymes involved in oxidative defense mechanism in conditions of carbon tetrachloride (CCl (4)) -induced rat liver toxicity. To carry out the study, rats were divided into four groups: group I (normal control), group II (CCl (4) treated), group III (zinc control), and group IV (zinc + CCl (4) treated). Animals in group II and group IV were administered 0.1 mL of CCl (4) mixed with 0.1 mL of groundnut oil on alternate days for a period of 8 weeks. Zinc in the form of zinc sulphate was given to animals of group II and group IV at a dose level of 227 mg/L in drinking water. Animals given CCl (4) treatment alone showed a significant increase in the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and the concentration of malondialdehyde (MDA) product, whereas a significant depression was observed in the levels of reduced glutathione (GSH). Zinc treatment to CCl (4) -treated rats brought the altered levels of GSH, MDA, and SOD as observed following CCl (4) -treatment alone to within normal limits. However, the activities of catalase and glutathione peroxidase, which were increased under carbon tetrachloride treatment, were significantly attenuated and tended to become normal. Hence, the present study suggests that zinc may play an important role in regulating the activities of the enzymes involved in antioxidative defense system under CCl (4) toxic conditions.
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Affiliation(s)
- D Dhawan
- Department of Biophysics, Panjab University, Chandigarh160014, India
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Singh K, Ahluwalia P. Effect of monosodium glutamate on lipid peroxidation and certain antioxidant enzymes in cardiac tissue of alcoholic adult male mice. J Cardiovasc Dis Res 2012; 3:12-8. [PMID: 22346139 PMCID: PMC3271674 DOI: 10.4103/0975-3583.91595] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Monosodium glutamate (MSG), a sodium salt of glutamic acid is commonly used as flavor enhancer in Chinese, Japanese and ready to serve foods all over the World, is the inducer of oxidative stress. In the present era, MSG and alcohol is becoming a part of daily food. Concomitantly, there is a tremendous increase in the incidences of cardiovascular diseases. So, the present study was designed to elucidate the effect of MSG by evaluating the changes in oxidative stress markers in cardiac tissue of normal and alcoholic adult male mice. MATERIALS AND METHODS Animals were divided into six groups of six mice each and MSG at dose levels of 0, 4, and 8 mg/g body weight was given orally for seven consecutive days (that is from 31st day to 37(th) day of alcohol ingestion) to chronic alcoholic (30% ethanol/100 g body weight) adult male mice. After the dose period (38(th) day), animals were fasted overnight, sacrificed by decapitation and hearts were removed for the estimation of lipid peroxidation (LPO), xanthine oxidase (XOD), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) and its metabolizing enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR). RESULTS A significant (P < 0.001) increase was observed in LPO and XOD levels while a significant decrease (P < 0.001) in the levels of SOD, CAT, GSH, GPx and GR was found in cardiac tissue of normal and alcoholic animals. CONCLUSION These observations suggested that oral ingestion of MSG at dose levels of 4 mg/g body weight and above with and without alcohol increased the oxidative stress and thereby, could act as an additional factor for the initiation of atherosclerosis.
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Affiliation(s)
- Kuldip Singh
- Department of Biochemistry, Govt. Medical College – Amritsar, India
| | - Pushpa Ahluwalia
- Department of Biochemistry, Panjab University, Chandigarh, India
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Singh K, Kaur J, Ahluwalia P, Sharma J. Effect of monosodium glutamate on various lipid fractions and certain antioxidant enzymes in arterial tissue of chronic alcoholic adult male mice. Toxicol Int 2012; 19:9-14. [PMID: 22736896 PMCID: PMC3339252 DOI: 10.4103/0971-6580.94507] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Oral ingestion of monosodium glutamate (MSG) to chronic alcoholic adult male mice at dose levels of 4 and 8 mg/g body weight for seven consecutive days caused a significant increase in lipid fractions, lipid peroxidation, xanthine oxidase, whereas the levels of superoxide dismutase, catalase, glutathione, and its metabolizing enzymes like glutathione peroxidase and glutathione reductase were significantly decreased in the arterial tissue. These observations suggested that ingestion of MSG to chronic alcoholic animals had no beneficial effect and thereby, could act as an additional factor for the initiation of atherosclerosis.
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Affiliation(s)
- Kuldip Singh
- Department of Biochemistry, Government Medical College, Amritsar -143001, India
| | - Jaspinder Kaur
- Department of Biochemistry, Government Medical College, Amritsar -143001, India
| | - P. Ahluwalia
- Department of Biochemistry, Panjab University, Chandigarh – 160014, India
| | - Jyoti Sharma
- Department of Biochemistry, Panjab University, Chandigarh – 160014, India
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Resistance of erythrocytes from brown trout (Salmo trutta m. trutta L.) affected by ulcerative dermal necrosis syndrome. Pol J Vet Sci 2011; 14:443-8. [PMID: 21957739 DOI: 10.2478/v10181-011-0065-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In the present work we evaluated the effect of ulcerative dermal necrosis (UDN) syndrome on resistance of erythrocytes to haemolytic agents and lipid peroxidation level in the blood from brown trout (Salmo trutta m. trutta L.). Results showed that lipid peroxidation increased in erythrocytes, as evidenced by high thiobarbituric acid reactive substance (TBARS) levels. Compared to control group, the resistance of erythrocytes to haemolytic agents was significantly lower in UDN-positive fish. Besides, UDN increased the percent of hemolysated erythrocytes subjected to the hydrochloric acid, urea and hydrogen peroxide. Results showed that UDN led to an oxidative stress in erythrocytes able to induce enhanced lipid peroxidation level, as suggested by TBARS level and decrease of erythrocytes resistance to haemolytic agents.
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Gargouri B, Nasr R, Mseddi M, Benmansour R, Lassoued S. Induction of Epstein-Barr virus (EBV) lytic cycle in vitro causes lipid peroxidation, protein oxidation and DNA damage in lymphoblastoid B cell lines. Lipids Health Dis 2011; 10:111. [PMID: 21722381 PMCID: PMC3146848 DOI: 10.1186/1476-511x-10-111] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2011] [Accepted: 07/01/2011] [Indexed: 12/15/2022] Open
Abstract
Background We investigated the oxidative modifications of lipids, proteins and DNA, potential molecular targets of oxidative stress, in two lymphoblastoid cell lines: B95-8 and Raji, after EBV lytic cycle induction. Conjugated dienes level was measured as biomarker of lipid peroxidation. Malondialdehyde adduct and protein carbonyl levels, as well as protein thiol levels were measured as biomarkers of protein oxidation. DNA fragmentation was evaluated as biomarker of DNA oxidation. Results After 48 h (peak of lytic cycle), a significant increase in conjugated dienes level was observed in B95-8 and Raji cell lines (p = 0.0001 and p = 0.019 respectively). Malondialdehyde adduct, protein carbonyl levels were increased in B95-8 and Raji cell lines after EBV lytic cycle induction as compared to controls (MDA-adduct: p = 0.008 and p = 0.006 respectively; Carbonyl: p = 0.003 and p = 0.0039 respectively). Proteins thiol levels were decreased by induction in B95-8 and Raji cell lines (p = 0.046; p = 0.002 respectively). DNA fragmentation was also detected in B95-8 and Raji cell lines after EBV lytic cycle induction as compared to controls. Conclusion The results of this study demonstrate the presence of increased combined oxidative modifications in lipids, proteins in B95-8 and Raji cells lines after EBV lytic cycle induction. These results suggest that lipid peroxidation, protein oxidation and DNA fragmentation are generally induced during EBV lytic cycle induction and probably contribute to the cytopathic effect of EBV.
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Affiliation(s)
- Bochra Gargouri
- Unité de Biotechnologie et Pathologies, Institut Supérieur de Biotechnologie de Sfax, Tunisia.
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Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans. Eur J Appl Physiol 2010; 111:1127-33. [DOI: 10.1007/s00421-010-1738-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/10/2010] [Indexed: 12/22/2022]
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Polish mother and child cohort study--defining the problem, the aim of the study and methodological assumption. Int J Occup Med Environ Health 2010; 22:383-91. [PMID: 20053622 DOI: 10.2478/v10001-009-0037-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVES Exposures during prenatal period have implications for pregnancy outcome as well as for children's health, morbidity and mortality. Prospective cohort study design allows for the identification of exposures that may influence pregnancy outcome and children's health, verification of such exposures by biomarker measurements and notification of any changes in exposure level. MATERIALS AND METHODS Polish Mother and Child Cohort Study (REPRO_PL) is multicenter prospective cohort study conducted in 8 different regions of Poland. The final cohort is intended to comprise 1300 mother-child pairs to be recruited within 4-year period (2007-2011). The recruitment and all scheduled visits are conducted in maternity units or clinics in the districts included in the study. The women are followed-up 3 times in pregnancy (once in each trimester) and after delivery for the notification of pregnancy outcome. During each visit, detailed questionnaire and biological samples are collected including saliva, urine, hair, maternal blood and cord blood. About 6 weeks postpartum, breast milk from part of the women is collected. The study concentrates on the identification and evaluation of the effects of prenatal environmental exposure on pregnancy outcome and children's health. Specific research hypotheses refer to the role of heavy metals, exposure to polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) in the aetiology of small-for-gestational-age (SGA) and preterm delivery (PD). The role of oxidative stress putative mechanism and pregnant women nutritional status will be investigated. Based on questionnaire data, the impact of occupational exposures and stressful situations will be evaluated. RESULTS The results of the study will become available within the next few years and will help to determine levels of child prenatal exposure in several areas of Poland and its impact on course and outcome of pregnancy.
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Tunc T, Demirin H, Karaoglu A, Kesik V, Temiz A, Ozler M, Sadir S, Atabek C, Kul M, Oztas E, Korkmaz A. Evaluation of effects of s-methyl isothiourea and melatonin on intestinal ischemia/reperfusion injury in rats. Fetal Pediatr Pathol 2010; 29:212-23. [PMID: 20594145 DOI: 10.3109/15513811003786319] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The present study was designed to evaluate whether the administration of s-methylisothiourea and melatonin has protective potential in intestinal ischemia/reperfusion injury. Forty male Sprague-Dawley rats were divided into five groups. Ileal specimens were obtained to determine the levels of malondialdehyde, protein carbonyl content, levels of antioxidant enzymes and evaluation of histologic changes. Combination of s-methylisothiourea and melatonin, led to a statistically significant increase in activities of antioxidant enzymes with a decrease in malondialdehyde and protein carbonyl content and intestinal mucosal injury scores. It was shown; combination of SMT and melatonin may exert more promised results.
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Affiliation(s)
- Turan Tunc
- Department of Pediatrics, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey.
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Vakilian K, Ranjbar A, Zarganjfard A, Mortazavi M, Vosough-Ghanbari S, Mashaiee S, Abdollahi M. On the relation of oxidative stress in delivery mode in pregnant women; a toxicological concern. Toxicol Mech Methods 2009; 19:94-9. [PMID: 19778252 DOI: 10.1080/15376510802232134] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The objective was to investigate the effect two modes of labor (vaginal delivery and elective cesarean section) on thiobarbituric reactive substances (TBARS) as markers of lipid peroxidation, total antioxidant power (ferric reducing ability, TAP), and total thiol molecules (TTM) in blood of mothers and their newborns. One hundred and twenty women with normal pregnancy and normal blood biochemical parameters were divided into groups of vaginal delivery (VD) and elective cesarean surgery (ECS). Blood samples were obtained firstly in the time 37-40 weeks of pregnancy and secondly during labor phase for VD or during ECS. Blood samples from umbilical cord arterial of newborns were also obtained at birth after separation of cord. Plasma levels of TBARS, TAP, and TTM were determined. There was no significant differences between VD and ECS mothers before labor in plasma levels of TBARS, TTM, and TAP. Mothers in the VD group showed a significant increase in TBARS (p < 0.05) after delivery. And TTM level showed a significant increase in ECS group (p < 0.05) as compared to pre-delivery levels. Comparing oxidative stress variables between VD and ECS groups after labor, plasma levels of TBARS, and TTM significantly increased (p < 0.05) in VD mothers. TAP was not significantly different between VD and ECS groups. Newborn of VD mothers showed a significant increase in TBARS (p < 0.05), and TAP (p < 0.05) as compared to newborn of ECS. TTM was not significantly different between two groups of newborns. The results indicate that mothers in VD and their newborns are in more oxidative stress than those who underwent ECS for delivery. Linking oxidative stress to severe neonatal diseases, it may be reasonable to assess whether antioxidant supplementation during pregnancy may reduce the frequency of neonatal diseases.
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Affiliation(s)
- Katayun Vakilian
- School of Paramedical Sciences, Arak University of Medical Sciences, Arak, Iran
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Kumaran VS, Arulmathi K, Kalaiselvi P. Senescence mediated redox imbalance in cardiac tissue: Antioxidant rejuvenating potential of green tea extract. Nutrition 2009; 25:847-54. [DOI: 10.1016/j.nut.2009.02.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2008] [Revised: 02/15/2009] [Accepted: 02/16/2009] [Indexed: 01/01/2023]
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Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol 2009; 83:519-48. [PMID: 19448996 DOI: 10.1007/s00204-009-0432-0] [Citation(s) in RCA: 437] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2009] [Accepted: 04/28/2009] [Indexed: 02/06/2023]
Abstract
Reactive oxygen species (ROS) are highly reactive molecules that are naturally generated in small amounts during the body's metabolic reactions and can react with and damage complex cellular molecules such as lipids, proteins, or DNA. Acute and chronic ethanol treatments increase the production of ROS, lower cellular antioxidant levels, and enhance oxidative stress in many tissues, especially the liver. Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces liver injury. Many pathways play a key role in how ethanol induces oxidative stress. This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced liver injury. Special emphasis is placed on CYP2E1, which is induced by alcohol and is reactive in metabolizing and activating many hepatotoxins, including ethanol, to reactive products, and in generating ROS.
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Affiliation(s)
- Arthur I Cederbaum
- Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA.
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Brzeszczynska J, Pieniazek A, Gwozdzinski L, Gwozdzinski K, Jegier A. Structural alterations of erythrocyte membrane components induced by exhaustive exercise. Appl Physiol Nutr Metab 2008; 33:1223-31. [DOI: 10.1139/h08-125] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Physical exercise was used as a model of the physiological modulator of free radical production to examine the effects of exercise-induced oxidative modifications on the physico-biochemical properties of erythrocyte membrane. The aim of our work was to investigate conformational changes of erythrocyte membrane proteins, membrane fluidity, and membrane susceptibility to disintegration. Venous blood was taken before, immediately after, and 1 h after an exhaustive incremental cycling test (30 W·min–1ramp), performed by 11 healthy untrained males on balanced diets (mean age, 22 ± 2 years; mean body mass index, 25 ± 4.5 kg·m–2). In response to this exercise, individual maximum heart rate was 195 ± 12 beats·min–1and maximum wattage was 292 ± 27 W. Electron paramagnetic resonance spectroscopy was used to investigate alterations in membrane proteins and membrane dynamics, and to measure production of radical species. The reducing potential of plasma (RPP) was measured using the reduction of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the ferric-reducing ability of plasma. Exercise induced decreases in erythrocyte membrane fluidity in the polar region (p < 0.0001) and alterations in the conformational state of membrane proteins (p < 0.05). An increase in RPP was observed immediately after exercise (p < 0.001), with a further increase 1 h postexercise (p < 0.0001). Supporting measurements of lipid peroxidation showed an increase in thiobarbituric acid reactive substances immediately after exercise (p < 0.05) and at 1 h of recovery (p < 0.001); however, free radicals were not detected. Results indicate the existence of early postexercise mild oxidative stress after single-exercise performance, which induced structural changes in erythrocyte membrane components (protein aggregation) and in the membrane organization (lipids rigidization) that followed lipid peroxidation but did not lead to cellular hemolysis.
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Affiliation(s)
- Joanna Brzeszczynska
- School of Life Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK
- Department of Biophysics, Medical University of Lodz, 90-643 Lodz, Poland
- Department of Sports Medicine, Medical University of Lodz, 90-647 Lodz, Poland
| | - Anna Pieniazek
- School of Life Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK
- Department of Biophysics, Medical University of Lodz, 90-643 Lodz, Poland
- Department of Sports Medicine, Medical University of Lodz, 90-647 Lodz, Poland
| | - Lukasz Gwozdzinski
- School of Life Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK
- Department of Biophysics, Medical University of Lodz, 90-643 Lodz, Poland
- Department of Sports Medicine, Medical University of Lodz, 90-647 Lodz, Poland
| | - Krzysztof Gwozdzinski
- School of Life Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK
- Department of Biophysics, Medical University of Lodz, 90-643 Lodz, Poland
- Department of Sports Medicine, Medical University of Lodz, 90-647 Lodz, Poland
| | - Anna Jegier
- School of Life Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK
- Department of Biophysics, Medical University of Lodz, 90-643 Lodz, Poland
- Department of Sports Medicine, Medical University of Lodz, 90-647 Lodz, Poland
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Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 2008; 44:723-38. [PMID: 18078827 PMCID: PMC2268632 DOI: 10.1016/j.freeradbiomed.2007.11.004] [Citation(s) in RCA: 578] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2007] [Revised: 11/02/2007] [Accepted: 11/05/2007] [Indexed: 12/11/2022]
Abstract
Ethanol-induced oxidative stress seems to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway seems to be the induction of cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide and, in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This review article summarizes some of the biochemical and toxicological properties of CYP2E1 and briefly describes the use of cell lines developed to constitutively express CYP2E1 and CYP2E1 knockout mice in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help us to understand the actions of CYP2E1 and its role in alcoholic liver injury.
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Affiliation(s)
- Yongke Lu
- Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
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Umarani M, Shanthi P, Sachdanandam P. Protective effect of Kalpaamruthaa in combating the oxidative stress posed by aflatoxin B1-induced hepatocellular carcinoma with special reference to flavonoid structure-activity relationship. Liver Int 2008; 28:200-13. [PMID: 18251979 DOI: 10.1111/j.1478-3231.2007.01615.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
AIMS/BACKGROUND Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. It has been postulated to play a major role in the aetiology of primary human liver cancer. Lipid peroxidation (LPO) is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. The present investigation aimed at assessing the effect of Kalpaamruthaa (KA), a modified Siddha preparation, on AFB1-mediated hepatocellular carcinoma (HCC). METHODS The drug was administered orally (300 mg/kg body weight/day) for 28 days to HCC-bearing rats. The level of lipid peroxides, antioxidant enzymes, glutathione and glutathione-metabolizing enzyme activity were determined in the plasma, haemolysate and liver homogenate of control and experimental rats. RESULTS Rats subjected to AFB1showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of enzymic and non-enzymic antioxidant and glutathione-metabolizing enzyme levels. KA treatment restored the deranged LPO and enzyme activities almost to control levels, thereby suggesting hepatoprotection. CONCLUSION This study highlighted the beneficial effect of KA in reversing the damage posed by AFB1 and thereby bringing about an improvement in the antioxidant status to combat the oxidative stress.
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Affiliation(s)
- Mohanasundaram Umarani
- Department of Medical Biochemistry, Dr A. L. Mudaliar Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
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Méndez-Armenta M, Ríos C. Cadmium neurotoxicity. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2007; 23:350-8. [PMID: 21783780 DOI: 10.1016/j.etap.2006.11.009] [Citation(s) in RCA: 223] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2006] [Revised: 09/20/2006] [Accepted: 11/22/2006] [Indexed: 05/18/2023]
Abstract
The Cd has been recognized as one of the most toxic environmental and industrial pollutants due to its ability to induce disturbances in several organs and tissues following either acute or chronic exposure. This review accounts for the recent evidence on its mechanisms to induce neurotoxicity, the role of the blood-brain barrier, oxidative stress, interference with calcium, and zinc-dependent processes and apoptosis induction as well as the modulatory effect of metallothionein. Discussion about cadmium neurotoxicity is centered on mechanisms of induction of cellular disfunctions. Future investigations must address those neuronal mechanisms in detail in order to understand cadmium-induced neurotoxicity.
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Affiliation(s)
- Marisela Méndez-Armenta
- Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama Tlalpan C.P. 14269, D.F., Mexico
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Subramanian S, Rajendiran G, Sekhar P, Gowri C, Govindarajulu P, Aruldhas MM. Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiata Geoffrey). Reversible oxidative stress in the semen. Toxicol Appl Pharmacol 2006; 215:237-49. [PMID: 16678873 DOI: 10.1016/j.taap.2006.03.004] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2005] [Revised: 02/20/2006] [Accepted: 03/14/2006] [Indexed: 11/19/2022]
Abstract
The present study was designed to test the hypothesis that oxidative stress mediates chromium-induced reproductive toxicity. Monthly semen samples were collected from adult monkeys (Macaca radiata), which were exposed to varying doses (50, 100, 200 and 400 ppm) of chromium (as potassium dichromate) for 6 months through drinking water. Chromium treatment decreased sperm count, sperm forward motility and the specific activities of antioxidant enzymes, superoxide dismutase and catalase, and the concentration of reduced glutathione in both seminal plasma and sperm in a dose- and duration-dependent manner. On the other hand, the quantum of hydrogen peroxide in the seminal plasma/sperm from monkeys exposed to chromium increased with increasing dose and duration of chromium exposure. All these changes were reversed after 6 months of chromium-free exposure period. Simultaneous supplementation of vitamin C (0.5 g/L; 1.0 g/L; 2.0 g/L) prevented the development of chromium-induced oxidative stress. Data support the hypothesis and show that chronic chromium exposure induces a reversible oxidative stress in the seminal plasma and sperm by creating an imbalance between reactive oxygen species and antioxidant system, leading to sperm death and reduced motility of live sperm.
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Affiliation(s)
- Senthivinayagam Subramanian
- Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-600 113, India.
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Mutlu-Türkoğlu U, Akalin Z, Ilhan E, Yilmaz E, Bilge A, Nişanci Y, Uysal M. Increased plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in patients with angiographically defined coronary artery disease. Clin Biochem 2005; 38:1059-65. [PMID: 16226736 DOI: 10.1016/j.clinbiochem.2005.07.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2004] [Revised: 06/06/2005] [Accepted: 07/06/2005] [Indexed: 10/25/2022]
Abstract
We investigated the oxidative modifications of lipids, proteins and DNA, three potential molecular targets of oxidative stress, in 30 patients with angiographically defined coronary artery disease (CAD) and 30 healthy control subjects. In addition, we examined relationships between these oxidative modifications and the severity of vascular lesions in patients with CAD. Malondialdehyde (MDA) and protein carbonyl (PC) levels, as well as ferric reducing antioxidant power (FRAP), were measured in the plasma. DNA damage was evaluated as single strand breaks (SSBs), formamidopyrimidine glycosylase (Fpg) and endonuclease III (E-III)-sensitive sites by the comet assay in DNA isolated from lymphocytes. MDA and PC levels increased, but FRAP values decreased, in patients as compared to controls. However, these values did not vary with the number of affected coronary vessels and were not correlated with Duke score, a parameter of the severity of vascular lesions in patients with CAD. We also found that lymphocyte DNA damage (SSBs, Fpg and E-III sites) were increased in patients. Although there were no significant differences in SSBs values in patients grouped according to affected vessel number, Fpg and E-III sites increased. We also detected significant correlations between Duke scores and SSBs and Fpg sites. Serum cholesterol, triglyceride and LDL-cholesterol levels were found to increase, but HDL-cholesterol levels decreased in CAD patients, but these lipids were not correlated with Duke scores. The results of this study reinforce the presence of increased combined oxidative modifications in lipid, protein and DNA in patients with CAD. However, lymphocyte DNA damage seems to be a more reliable assay than MDA and PC determinations to detect the severity of vascular lesions in patients.
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Affiliation(s)
- Umit Mutlu-Türkoğlu
- Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, 34093 Capa-Istanbul, Turkey.
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Abstract
Reactive oxygen species are the major contributing factors to lung ischemia-reperfusion (IR) injury. In this study, we tested whether a water soluble antioxidant fullerene derivative [C(60)(ONO(2))(7 +/- 2)] attenuates IR lung injury. Young Wistar rats were divided into two groups: control and C(60)(ONO(2))(7 +/- 2). Under ventilation with 95% air-5% CO(2) gas mixture and a 2.5 cm H(2)O end-expiratory pressure, the isolated lungs were perfused with a physiological solution. The experimental protocol included three periods: baseline (10 min), ischemia (45 min) and reperfusion (60 min, ventilated with 95% O(2)-5% CO(2) gas mixture). Before and after ischemia, we measured pulmonary arterial pressure (Ppa), pulmonary venous pressure and lung weight (W). Then, pulmonary capillary pressure and filtration coefficient (K(fc)) were calculated. Ischemia caused increases in Ppa, W and K(fc) in the control group. For most cases, the above ischemia-induced increases were attenuated by the C(60)(ONO(2))(7 +/- 2) pretreatment. Our results suggest that the antioxidant C(60)(ONO(2))(7 +/- 2) attenuates IR-induced lung injury.
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Affiliation(s)
- Y-L Lai
- Department of Physiology, National Taiwan University College of Medicine, No. 1 Sec. 1, Jen-ai Road Taipei 100, Taiwan.
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Jara-Prado A, Ortega-Vazquez A, Martinez-Ruano L, Rios C, Santamaria A. Homocysteine-induced brain lipid peroxidation: effects of NMDA receptor blockade, antioxidant treatment, and nitric oxide synthase inhibition. Neurotox Res 2003; 5:237-43. [PMID: 12835115 DOI: 10.1007/bf03033381] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The effect of homocysteine (HCY) on lipid peroxidation (LP), a current mechanism of oxidative neurotoxicity, was investigated in rat brain synaptosomes. LP was assessed by measuring the amount of thiobarbituric acid-reactive substances (TBARS) formed from synaptosomal fractions following HCY treatment. Increasing HCY concentrations (5-1000 micro M) enhanced the TBARS formation in brain synaptosomes in a concentration-dependent manner. When compared at equimolar concentrations (100 micro M), the oxidative potency of HCY was lower than that of the oxidant ferrous sulfate, similar to that produced by glutamate (Glu) and the mitochondrial toxin 3-nitropropionic acid, and higher than that of the Glu agonists, kainate and quinolinate. The N-methyl-D-aspartate receptor (NMDAr) antagonist dizocilpine (MK-801) completely blocked the HCY-induced LP at concentrations between 5 to 1000 micro M, whereas the well-known antioxidant N-acetylcysteine (NAC) was less effective, but still protective against the HCY oxidative toxicity at higher concentrations (400 and 1000 micro M). Three nitric oxide synthase (NOS) inhibitors, 7-nitroindazole (7-NI), Nomega-nitro-L-arginine (L-NARG) and Nomega-nitro-L-arginine methyl ester (L-NAME), were also tested on HCY-induced LP at increasing concentrations. Both nonspecific NOS inhibitors (L-NARG and L-NAME) decreased more effectively the HCY-induced LP than did the selective neuronal NOS inhibitor, 7-NI. These results show that submillimolar concentrations of HCY can induce oxidative injury to nerve terminals, and this effect involves NMDAr stimulation, NOS activation, and associated free radicals formation.
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Affiliation(s)
- Aurelio Jara-Prado
- Departamento de Genetica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. Insurgentes Sur # 3877, México D.F., 14269, México
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Xie H, Rath NC, Huff GR, Balog JM, Huff WE. Inflammation-induced changes in serum modulate chicken macrophage function. Vet Immunol Immunopathol 2001; 80:225-35. [PMID: 11457476 DOI: 10.1016/s0165-2427(01)00260-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Inflammation-induced changes in serum protein profiles and the effects of such serum on a chicken macrophage cell line HD11 were studied to find whether the changes in serum affect cellular immunity. Four-week-old male broiler chickens were injected subcutaneously with either olive oil or 50% croton oil mixed in olive oil to induce inflammation. The birds were bled at 48h after injection, and serum protein profiles were compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric evaluation. At 48h post-injection the serum from croton oil-injected birds showed distinct changes in protein profiles characterized by a selective increase or decrease in levels of several serum proteins. The protein bands which showed increases had relative molecular weights (Mr) corresponding to 65kilo Daltons (kD), 42kD, and two or more proteins with Mr> or =200kD. The levels of serum albumin (49kD), and a 56kD protein were reduced in croton oil-injected birds. The modulating effects of such serum on HD11 cells were studied using bacterial lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) induced functional activation of these cells. The LPS-induced interleukin-6 (IL-6) production by HD11 cells was not affected by the presence of either olive oil-treated control or croton oil-treated inflammatory serum but nitrite production was enhanced by the inflammatory serum. Similarly, inflammatory serum also enhanced PMA-induced respiratory burst measured using dichlorofluorescein diacetate (DCF-DA) oxidation mediated by reactive oxygen intermediates. These results suggest that inflammatory serum can modulate macrophage function by influencing the production of reactive oxygen and nitrogen species which could affect their phagocytic and bactericidal activities.
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Affiliation(s)
- H Xie
- Poultry Production and Product Safety Research Unit, USDA, Agricultural Research Service, University of Arkansas, Fayetteville, AR 72701, USA
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Wada K, Miyazawa T, Nomura N, Yano A, Tsuzuki N, Nawashiro H, Shima K. Mn-SOD and Bcl-2 expression after repeated hyperbaric oxygenation. ACTA NEUROCHIRURGICA. SUPPLEMENT 2001; 76:285-90. [PMID: 11450026 DOI: 10.1007/978-3-7091-6346-7_59] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2023]
Abstract
To clarify the mechanism of ischemic tolerance induced by HBO, we investigated the effect of HBO on immunoreactivity to Bcl-2 and Bax, apoptosis-regulating protein, or Mn-SOD, a radical scavenging system, in the CA1 sector of the gerbil hippocampus. Pretreatment comprising, five sessions at 2 ATA (atmosphere absolute) every other day, but not that comprising, ten sessions at 3 ATA every day, caused significant increases in Bcl-2 and Mn-SOD immunoreactivity in the CA1 sector compared with in the sham pretreatment group. No significant differences in Bax immunoreactivity and neuronal density in the CA1 hippocampal neurons was observed between the groups. These results suggest that protection against mitochondrial alterations after ischemia through Mn-SOD and/or Bcl-2 expression is related to the ischemic tolerance induced by repeated HBO pre-treatment.
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Affiliation(s)
- K Wada
- Department of Neurosurgery, National Defense Medical College, Saitama, Japan
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Wada K, Miyazawa T, Nomura N, Tsuzuki N, Nawashiro H, Shima K. Preferential Conditions for and Possible Mechanisms of Induction of Ischemic Tolerance by Repeated Hyperbaric Oxygenation in Gerbil Hippocampus. Neurosurgery 2001. [DOI: 10.1227/00006123-200107000-00025] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Wada K, Miyazawa T, Nomura N, Tsuzuki N, Nawashiro H, Shima K. Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in gerbil hippocampus. Neurosurgery 2001; 49:160-6; discussion 166-7. [PMID: 11440438 DOI: 10.1097/00006123-200107000-00025] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE We reported previously that repeated hyperbaric oxygenation (HBO) as pretreatment induced ischemic tolerance in the gerbil hippocampus. This study was conducted to determine the preferential conditions for induction of ischemic tolerance by HBO and the mechanism of this induction through immunohistochemical analysis of Bcl-2, Bax, and manganese superoxide dismutase expression. METHODS Five-minute forebrain ischemia was produced in gerbils after pretreatment with 2 atmospheres absolute (ATA) HBO once every other day for one, three, or five sessions, 2 ATA hyperbaric air once every other day for five sessions, or 3 ATA HBO once daily for 10 sessions. Histological examinations were then performed. Two days after pretreatment with 2 ATA HBO once every other day for five sessions or with 3 ATA HBO once daily for 10 sessions, sections were analyzed immunohistochemically. RESULTS Pretreatment with 2 ATA HBO once every other day for three or five sessions induced ischemic tolerance; however, pretreatment with 2 ATA HBO for one session, 2 ATA hyperbaric air once every other day for five sessions, or 3 ATA HBO once daily for 10 sessions did not. Pretreatment with 2 ATA HBO once every other day for five sessions, but not with 3 ATA HBO once daily for 10 sessions, significantly increased Bcl-2 and manganese superoxide dismutase immunoreactivity in the CA1 sector. CONCLUSION These results suggest that protection against mitochondrial alterations after ischemia through manganese superoxide dismutase and/or Bcl-2 expression may be related to induction of ischemic tolerance by repeated HBO pretreatment.
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Affiliation(s)
- K Wada
- Undersea Medical Center, Japan Maritime Self Defense Force, Kanagawa.
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Durot I, Maupoil V, Ponsard B, Cordelet C, Vergely-Vandriesse C, Rochette L, Athias P. Oxidative injury of isolated cardiomyocytes: dependence on free radical species. Free Radic Biol Med 2000; 29:846-57. [PMID: 11063910 DOI: 10.1016/s0891-5849(00)00382-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The contribution of lipid peroxidation to myocardial injury by free radicals (FR) is still unclear. Consequently, we examined the functional damages inflicted on cultured rat cardiomyocytes (CM) during FR stress provoked by the xanthine/xanthine oxidase system (X/XO) or by a hydroperoxidized fatty acid ((9 Z, 11 E, 13 (S), 15 Z)-13-hydroperoxyocta-decatrienoic acid; 13-HpOTrE), in order to simulate in vitro the initial phase and the propagation phase of the FR attack, respectively. Transmembrane potentials were recorded with glass microelectrodes and contractions were monitored photometrically. The EPR spectroscopy showed that X/XO produced superoxide and hydroxyl radicals during 10 min. The X/XO system altered sharply and irreversibly the spontaneous electrical and mechanical activities of the CM. However, the gas chromatographic analysis showed that these drastic functional damages were associated with comparatively moderate membrane PUFA degradation. Moreover, the EPR analysis did not reveal the production of lipid-derived FR. 13-HpOTrE induced a moderate and reversible decrease in electrical parameters, with no change in CM contractions. These results indicate that the functional consequences of FR attack are dependent on the radical species present and do not support the idea that the membrane lipid breakdown is a major factor of myocardial oxidant dysfunction.
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Affiliation(s)
- I Durot
- Laboratory of Cardiovascular Physiopathology and Pharmacology, Faculties of Medicine and Pharmacy, 21079, Dijon, France
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Lukienko PI, Mel'nichenko NG, Zverinskii IV, Zabrodskaya SV. Antioxidant properties of thiamine. Bull Exp Biol Med 2000. [DOI: 10.1007/bf02682257] [Citation(s) in RCA: 72] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Gupte SA, Okada T, Tateyama M, Ochi R. Activation of TxA2/PGH2 receptors and protein kinase C contribute to coronary dysfunction in superoxide treated rat hearts. J Mol Cell Cardiol 2000; 32:937-46. [PMID: 10888248 DOI: 10.1006/jmcc.2000.1134] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We have previously shown that superoxide anion (O2-) stimulates the release of vasoconstrictor prostanoids and induces a prolonged rise in coronary perfusion pressure (CPP) that persists even after removal of O2-. In this study, we tested the hypothesis that the increased CPP is mediated by activation of TxA2/ PGH2 (TP) receptors and protein kinase C (PKC)-dependent mechanisms. In Langendorff perfused rat hearts, O2- was applied for 15 min and then washed out over a period of 20 min. Application of O2- increased the release of vasoconstrictive (TxA2 and PGF2alpha) and decreased vasodilating (PGI2 and PGE2) prostanoids. Although indomethacin (10 microM), a cyclooxygenase inhibitor, attenuated the rise in CPP during O2- perfusion, the increase was not completely blocked. OKY 046Na (10 microM), a thromboxane synthase inhibitor, had no effect on O2--induced increases in CPP, whereas ONO 3708 (10 microM), a TP receptor antagonist, suppressed this effect. PKC activity was also elevated by more than 50% by O2- perfusion. CPP typically increased throughout the O2- wash-out. This post-O2- vasoconstriction was not inhibited by indomethacin, nitroglycerin or nitrendipine. In contrast, ONO 3708 (10 microM) and two PKC inhibitors, staurosporine (10 nM) and calphostin C (100 nM), completely blocked the rise in CPP, and even elicited vasodilation. PDBu enhanced the post-O2- vasoconstriction. We conclude that O2--induced coronary vasoconstriction is initially mediated by TP receptors, but activation of PKC sustains the response.
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Affiliation(s)
- S A Gupte
- Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan.
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Sondeen JL, Dubick MA, Yu Y, Majumdar AP. Hemorrhage and renal ischemia-reperfusion upregulates the epidermal growth factor receptor in rabbit duodenum. THE JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1999; 134:641-8. [PMID: 10595793 DOI: 10.1016/s0022-2143(99)90105-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
To study the role of EGF-R in small intestinal adaptation to hemorrhage and I/R, anesthetized rabbits were implanted aseptically with arterial and venous catheters and bilateral renal artery Doppler flow probes and silastic occluders and allowed to recover. Rabbits were then randomly assigned to one of six groups: time control; hemorrhage (22.5 mL/kg) and 2.5 hours of renal occlusion (hemorrhage plus I/R); hemorrhage plus I/R and 2:1 LRS resuscitation; hemorrhage plus I/R and 3:1 LRS resuscitation; hemorrhage alone; or I/R alone. Rabbits were killed 48 hours after hemorrhage, and a section of duodenum was collected for analysis. Hemorrhage plus I/R induced a 2.5-fold increase in EGF-R tyrosine kinase activity compared with that found in the control group (P < .05), and this effect was not modified by either LRS resuscitation regimen. This increased activity was associated with similar Increases in EGF-R protein concentrations and approximately a 50% increase in EGF-R messenger (m)RNA levels compared with levels found in the control group. Further analysis of possible regulatory mechanisms for the increased EGF-R expression after hemorrhage plus I/R detected higher levels of EGF-R phosphorylation compared with those found in the control group but no significant increases in transforming growth factor-alpha mRNA levels. These data, coupled with a significant increase in duodenal thlobarbituric acid-reactive substance concentrations from rabbits in the hemorrhage plus I/R group, support the hypothesis that tyrosine kinase signal transduction pathways involving the EGF-R are activated in the small intestine after hemorrhage, renal I/R, or both, and this process may be mediated, at least in part, by oxidant stress.
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Affiliation(s)
- J L Sondeen
- US Army Institute of Surgical Research, Fort Sam Houston, TX 78234-6315, USA
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Premalatha B, Sachdanandam P. Semecarpus anacardium L. nut extract administration induces the in vivo antioxidant defence system in aflatoxin B1 mediated hepatocellular carcinoma. JOURNAL OF ETHNOPHARMACOLOGY 1999; 66:131-139. [PMID: 10433469 DOI: 10.1016/s0378-8741(99)00029-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
The antioxidant defence system which plays a critical role in carcinogenesis is severely altered in aflatoxin B1 induced hepatocellular carcinoma conditions. In order to assess the antitumour activity of Semecarpus anacardium nut extract, a flavonoid containing drug, non-enzymic antioxidant levels were analysed in control and experimental animals. Plasma was analysed for uric acid, vitamin E and vitamin C. Glutathione, total thiols, non-protein thiols, vitamin E, vitamin C and cytochrome P450 were estimated in liver and kidney homogenates. Depletion of all these antioxidants were recorded in cancer conditions. These deleterious effects are controlled by the administration of Semecarpus anacardium nut extract. Following drug administration, there was a marked increase in antioxidant levels and a dramatic elevation in cytochrome P450 content. It can be concluded that the observed anticancer property of Semecarpus anacardium nut extract may also be explained by its strong antioxidant capacity and capability to induce the in vivo antioxidant system.
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Affiliation(s)
- B Premalatha
- Department of Medical Biochemistry, Dr. A.L.M.P-G I.B.M.S., University of Madras, Chennai, India.
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Charon I, Zuin-Kornmann G, Bataillé S, Schorderet M. Protective effect of neurotrophic factors, neuropoietic cytokines and dibutyryl cyclic AMP on hydrogen peroxide-induced cytotoxicity on PC12 cells: a possible link with the state of differentiation. Neurochem Int 1998; 33:503-11. [PMID: 10098719 DOI: 10.1016/s0197-0186(98)00056-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
We present evidence that the survival of PC12 cells exposed to hydroxyl radicals generated by hydrogen peroxide applied for 30 min at 1 mM was effective when they were differentiated in response to Nerve Growth Factor (NGF) and/or other inducers of neurite outgrowth such as basic-fibroblast growth factor and dibutyryl cyclic AMP. The time- and dose-dependent differentiation triggered by NGF was (1) markedly increased by basic fibroblast growth factor, interleukin-6 or dibutyryl cyclic AMP; (2) diminished by leukemia inhibitory factor or ciliary neurotrophic factor; (3) not potentiated by insulin-like growth factor I or progesterone. The influence of these various factors and agents on PC12 cells was evaluated by the estimation of neurite outgrowth, whereas their possible protective effects were assessed by the measurement of cell survival. Our results would indicate that the factors and agents that induced differentiation were also able to protect the cells against an oxidative stress.
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Affiliation(s)
- I Charon
- Department of Pharmacology, University Medical Center, Geneva, Switzerland
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Appenroth D, Winnefeld K. Vitamin E and C in the prevention of metal nephrotoxicity in developing rats. EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY : OFFICIAL JOURNAL OF THE GESELLSCHAFT FUR TOXIKOLOGISCHE PATHOLOGIE 1998; 50:391-6. [PMID: 9784013 DOI: 10.1016/s0940-2993(98)80024-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The protective effect of vitamin E and C on sodium chromate (Cr) and thallium (Tl) induced nephrotoxicity was tested in 10- and 55-day-old rats. The concentrations of Cr and Tl were determined in renal cortex and medulla by atomic absorption spectrometry. Urinary volume and protein excretion as well as blood urea nitrogen (BUN) concentration were determined as parameters of nephrotoxicity. Cr and Tl induced nephrotoxicity was significantly more expressed in adult than in young rats. In Cr and Tl nephrotoxicity the protective effect of vitamin E was evident in both age groups. Vitamin E decreased Tl concentration in renal tissue. Therefore its protective effect is not to be attributed to its known antioxidant effect but to lower Tl concentration in renal tissue. Vitamin C was protective in Cr and Tl induced nephrotoxicity in adult rats without influence on metal concentrations in renal tissue. The dose necessary for protection against toxic Cr action in adult rats was not tolerated by young rats. The combined administration of both vitamins abolished the protective effect against Cr nephrotoxicity of the administration of each vitamin alone in adult rats. When vitamin E and C were administered in Tl treated adult and young rats the protective effect was the same as after the administration of each vitamin alone. Possible mechanisms are discussed.
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Affiliation(s)
- D Appenroth
- Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany
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