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Elwany NE, El Salem A, Mostafa Mohamed N, Khalil SS, Mahmoud NM. Rebamipide protects against experimentally induced intestinal ischemia/reperfusion-promoted liver damage: Impact on SIRT1/β-catenin/FOXO1and NFκB signaling. Int Immunopharmacol 2023; 119:110269. [PMID: 37148771 DOI: 10.1016/j.intimp.2023.110269] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/20/2023] [Accepted: 04/28/2023] [Indexed: 05/08/2023]
Abstract
Rebamipide (Reba) is a well-known gastroprotective agent. However, its potential protective efficacy against intestinal ischemia/reperfusion (I/R)-induced liver injury remains elusive. Therefore, this study aimed to assess the modulatory effect of Reba on SIRT1/β-catenin/FOXO1-NFκB signaling cascade. Thirty-two male Wistar albino rats were randomized into four groups: G1 (sham): rats were subjected to surgical stress without I/R, GII (I/R): rats were subjected to 60 min/4-h I/R, GIII (Reba + I/R): rats received Reba 100 mg/kg/day, p.o. for three weeks, then were subjected to 60 min/4-h I/R, and GIV (Reba + EX527 + I/R): rats received Reba (100 mg/kg/day p.o.) + EX527 (10 mg/kg/day, ip) for three weeks before I/R. Reba pretreatment decreased the serum levels of ALT and AST, improved I/R-induced histological alterations of both intestine and liver, increased hepatic Silent information regulator 1 (SIRT1) expression/content, β-catenin expression/immunoreactivity, and FOXO1 expression, while suppressed NF-κB p65 expression/protein content. In addition, Reba increased hepatic total antioxidant capacity (TAC), while suppressed malondialdehyde (MDA), tumor necrosis factor (TNFα), and caspase-3 activity. Furthermore, Reba inhibited BAX expression, while upregulated Bcl-2 expression. Reba exhibited a plausible protective effect against intestinal I/R-mediated liver injury by modulating SIRT1/β-catenin/FOXO1-NFκB signaling mechanisms.
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Affiliation(s)
- Nisreen E Elwany
- Lecturer of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
| | - Amal El Salem
- Lecturer of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
| | | | - Sama S Khalil
- Associate professor of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
| | - Nevertyty M Mahmoud
- Lecturer of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
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Qiu S, Li X, Zhang J, Shi P, Cao Y, Zhuang Y, Tong L. Neutrophil membrane-coated taurine nanoparticles protect against hepatic ischemia-reperfusion injury. Eur J Pharmacol 2023; 949:175712. [PMID: 37054936 DOI: 10.1016/j.ejphar.2023.175712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 04/06/2023] [Accepted: 04/11/2023] [Indexed: 04/15/2023]
Abstract
Hepatic ischemia-reperfusion (I/R) injury is a multifactorial process caused by transient tissue hypoxia and the following reoxygenation, commonly occurring in liver transplantation and hepatectomy. Hepatic I/R can induce a systemic inflammatory response, liver dysfunction, or even multiple organ failure. Although we have previously reported that taurine could attenuate acute liver injury after hepatic I/R, only a tiny proportion of the systemically injected taurine could reach the targeted organ and tissues. In this present study, we prepared taurine nanoparticles (Nano-taurine) by coating taurine with neutrophil membranes and investigated the protective effects of Nano-taurine against I/R-induced injury and the underlying mechanisms. Our results showed that Nano-taurine restored liver function by declining AST and ALT levels and reducing histology damage. Nano-taurine decreased inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, NLR pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing CARD (ASC) and oxidants including superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and reactive oxygen species (ROS), exhibiting anti-inflammatory and antioxidant properties. The expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was increased, while prostaglandin-endoperoxide synthase 2 (Ptgs2) was decreased upon administration of Nano-taurine, suggesting that inhibiting ferroptosis may be involved in the mechanism during hepatic I/R injury. These results suggest that Nano-taurine have a targeted therapeutic effect on hepatic I/R injury by inhibiting inflammation, oxidative stress, and ferroptosis.
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Affiliation(s)
- Shijie Qiu
- Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, Heilongjiang Province, China
| | - Xuyi Li
- Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, Heilongjiang Province, China
| | - Jingyan Zhang
- Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, Heilongjiang Province, China
| | - Pilong Shi
- Department of Pharmacology, Daqing Campus, Harbin Medical University, Daqing, 163391, Heilongjiang Province, China
| | - Yonggang Cao
- Department of Pharmacology, Daqing Campus, Harbin Medical University, Daqing, 163391, Heilongjiang Province, China
| | - Yongzhi Zhuang
- Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, Heilongjiang Province, China.
| | - Liquan Tong
- Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, Heilongjiang Province, China.
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Aliyev SA, Aliyev ES. [Nasointestinal intubation in surgery of acute intestinal obstruction and peritonitis: past, present and future]. Khirurgiia (Mosk) 2021:92-99. [PMID: 34608786 DOI: 10.17116/hirurgia202110192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The authors analyze history of development nasointestinal intubation for abdominal decompression in patients acute intestinal obstruction and widespread peritonitis, contribution of Russian and foreign surgical schools to improvement and popularization of this technique. Advisability, clinical efficacy, advantages and disadvantages of this method are stated. The prospects of nasointestinal intubation in the foreseeable future are considered in these patients. Certain technical features of nasointestinal intubation and complications are described. The causes of negative attitude of foreign surgeons to nasointestinal intubation and motivation for refusing of this technique are discussed. Considering the arguments of supporters and opponents, the authors conclude that complete rejection of this technique is premature. A differentiated approach to nasointestinal intubation according to strict indications seems to be more legitimate than categorical rejection.
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Affiliation(s)
- S A Aliyev
- Azerbaijan Medical University, Baku, Azerbaijan
| | - E S Aliyev
- Azerbaijan Medical University, Baku, Azerbaijan
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Ahmadi S, Mehranjani MS. Taurine improves follicular survival and function of mice ovarian grafts through increasing CD31 and GDF9 expression and reducing oxidative stress and apoptosis. Eur J Pharmacol 2021; 903:174134. [PMID: 33940031 DOI: 10.1016/j.ejphar.2021.174134] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 04/21/2021] [Accepted: 04/26/2021] [Indexed: 10/21/2022]
Abstract
Ischemia-reperfusion (IR) injury is a major limitation of ovarian transplantation which threatens the follicular and graft survival. Taurine as a potent anti-oxidant, anti-apoptotic and anti-inflammatory agent, can prevent graft damages due to IR. We aimed to investigate the effect of taurine on the follicular survival and function of autotransplanted mouse ovaries. Female mice (4-5 weeks old) were divided into: control, autograft and autograft + taurine (200 mg/kg/day). The level of CD31 expression was evaluated two days (48 h) post transplantation. In addition, on day 7 post transplantation the serum levels of malondialdehyde (MDA) and the total antioxidant capacity (TAC) were assessed. Also, 28 days post transplantation; ovaries were studied stereologically and the percentage of apoptotic follicles, level of GDF9 expression and the serum concentrations of progesterone and estradiol were measured. Data were analyzed using one-way ANOVA and Tukey's test and the means were considered significantly different at P < 0.05. The total volume of the ovary (P < 0.01), volume of the cortex (P < 0.01) and medulla (P < 0.04), total number of different types of follicles, expression of GDF9 and CD31 and also the levels of progesterone, estradiol and TAC increased significantly in the autograft + taurine group compared to the autograft group (P < 0.001). The MDA level and apoptosis rate decreased significantly in the autograft + taurine group compared to the autograft group (P < 0.001). Taurine could significantly improve follicular survival and the function of grafted ovaries by accelerating the angiogenesis and reducing oxidative stress and apoptosis.
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Affiliation(s)
- Sepideh Ahmadi
- Department of Biology, Faculty of Science, Arak University, Arak, 381-5688138, Iran
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Kamel M, Ahmed SM, Abdelzaher W. The potential protective effect of modafinil in intestinal ischemic reperfusion-induced in rats. Int Immunopharmacol 2020; 88:106983. [PMID: 33182022 DOI: 10.1016/j.intimp.2020.106983] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 08/22/2020] [Accepted: 09/04/2020] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Intestinal ischemia reperfusion (IR) is a pathophysiologic process that leads to oxidative stress and acute inflammatory responses. Understanding the mechanisms explaining this inflammation is essential to developing therapeutic strategies. Therefore, the purpose of this study was to evaluate the protective outcome of modafinil (Mod) against intestinal damages caused by intestinal IR injury. METHODS/MATERIALS Fourty adult Male Wistar rats were randomly divided into four groups: sham control group; intestinal IR group; Mod pre-treated IR group and Mod post-treated IR group. Mod in a dose of 10 mg/kg was injected intraperitoneally once daily for 7 days pre or post IR treatment. RESULTS Mod significantly attenuated the IR induced elevations in intestinal malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin 1-β (IL-1β) and P-glycoprotein (P-gp) levels, caspase-3 activity. However, a significant increase in TAC was reported as compared with the IR group but its post-treated IR group was highly protective. Mod post-treatment down-regulated the IR induced cyclo-oxygenase-2 (COX-2) over-expression. Distorted mucosa with loss of surface epithelial cells, epithelial separation oedematous lamina propria and inflammatory cellular infiltration detected by histopathological examination of intestinal tissue, were markedly ameliorated by Mod post-treatment. On the other hand, Mod pre-treatment showed less protection against intestinal IR in rats. CONCLUSION Current study suggests that Mod post-treatment ameliorated intestinal damages, so it can be considered a potential therapeutic agent to protect against the major clinical challenge of intestinal injury resulting from IR.
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Affiliation(s)
- MahaYehia Kamel
- Department of Pharmacology, Faculty of Medicine, Minia University, Egypt
| | - Sabreen Mahmoud Ahmed
- Depatment of Human Anatomy and Embryology, Faculty of Medicine, Minia University, Delegated to Deraya University-New Minia City, Egypt
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Mousavi K, Niknahad H, Ghalamfarsa A, Mohammadi H, Azarpira N, Ommati MM, Heidari R. Taurine mitigates cirrhosis-associated heart injury through mitochondrial-dependent and antioxidative mechanisms. Clin Exp Hepatol 2020; 6:207-219. [PMID: 33145427 PMCID: PMC7592093 DOI: 10.5114/ceh.2020.99513] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 04/09/2020] [Indexed: 12/15/2022] Open
Abstract
Cirrhosis-induced heart injury and cardiomyopathy is a serious consequence of this disease. It has been shown that bile duct ligated (BDL) animals could serve as an appropriate experimental model to investigate heart tissue injury in cirrhosis. The accumulation of cytotoxic chemicals (e.g., bile acids) could also adversely affect the heart tissue. Oxidative stress and mitochondrial impairment are the most prominent mechanisms of bile acid cytotoxicity. Taurine (Tau) is the most abundant non-protein amino acid in the human body. The cardioprotective effects of this amino acid have repeatedly been investigated. In the current study, it was examined whether mitochondrial dysfunction and oxidative stress are involved in the pathogenesis of cirrhosis-induced heart injury. Rats underwent BDL surgery. BDL animals received Tau (50, 100, and 500 mg/kg, i.p.) for 42 consecutive days. A significant increase in oxidative stress biomarkers was detected in the heart tissue of BDL animals. Moreover, it was found that heart tissue mitochondrial indices of functionality were deteriorated in the BDL group. Tau treatment significantly decreased oxidative stress and improved mitochondrial function in the heart tissue of cirrhotic animals. These data provide clues for the involvement of mitochondrial impairment and oxidative stress in the pathogenesis of heart injury in BDL rats. On the other hand, Tau supplementation could serve as an effective ancillary treatment against BDL-associated heart injury. Mitochondrial regulating and antioxidative properties of Tau might play a fundamental role in its mechanism of protective effects in the heart tissue of BDL animals.
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Affiliation(s)
- Khadijeh Mousavi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Niknahad
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amin Ghalamfarsa
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamidreza Mohammadi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Reza Heidari
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Wen C, Guo Q, Wang W, Duan Y, Zhang L, Li J, He S, Chen W, Li F. Taurine Alleviates Intestinal Injury by Mediating Tight Junction Barriers in Diquat-Challenged Piglet Models. Front Physiol 2020; 11:449. [PMID: 32547405 PMCID: PMC7270355 DOI: 10.3389/fphys.2020.00449] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 04/09/2020] [Indexed: 12/28/2022] Open
Abstract
Background: Intestinal barrier contributes as an important role in maintaining intestinal homeostasis. Oxidative stress can cause critical damages in intestinal integrity of animals. Objectives: This study was conducted to investigate the alleviated effect of taurine against small intestine (duodenum, jejunum, ileum) injury induced by oxidative stress. Methods: The piglet model of diquat-induced oxidative stress was employed. In addition, analysis of intestinal morphology, reverse transcription PCR (RT-PCR), and Western blot were used in this study. Results: Compared with the control group (CON), diquat-induced oxidative stress triggers immune response; the content of immunoglobulin M (IgM) and immunoglobulin G (IgG) was significantly changed, but 0.60% taurine supplementation could restore the level of serum immunoglobulin. Oxidative stress induces serious damage in intestinal morphology structure and tight junction barrier. Compared with the CON, the villus height of intestine was significantly decreased, the crypt depth and villus height/crypt depth (V/C) were also decreased, and 0.60% taurine supplementation could restore impaired morphology and even improve crypt depth and V/C of the jejunum and ileum. Compared with the CON, oxidative stress markedly increased the messenger RNA (mRNA) expression level of claudin-1 and occludin in the duodenum, and the value of occludin was significantly decreased in the jejunum of the diquat group (DIQ). Relative to the DIQ, 0.60% taurine supplementation increased the mRNA expression level of claudin-1, occludin, and ZO-1 in the ileum. Compared with the CON, the expression of claudin-1 protein was significantly upregulated, and occludin and ZO-1 protein were both downregulated in the small intestine of DIQ. Conclusion: Taurine exerts protective effects by regulating immune response and restores the intestinal tight junction barrier when piglets suffer from oxidative stress.
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Affiliation(s)
- Chaoyue Wen
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
- Laboratory of Animal Nutrition and Human Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Science, Hunan Normal University, Changsha, China
| | - Qiuping Guo
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Wenlong Wang
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
- Laboratory of Animal Nutrition and Human Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Science, Hunan Normal University, Changsha, China
| | - Yehui Duan
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
| | - Lingyu Zhang
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Jianzhong Li
- Laboratory of Animal Nutrition and Human Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Science, Hunan Normal University, Changsha, China
| | - Shanping He
- Laboratory of Animal Nutrition and Human Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Science, Hunan Normal University, Changsha, China
| | - Wen Chen
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
| | - Fengna Li
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, China
- National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, China
- Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, China
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Toth S, Jonecova Z, Maretta M, Curgali K, Kalpakidis T, Pribula M, Kusnier M, Fagova Z, Fedotova J, La Rocca G, Rodrigo L, Caprnda M, Zulli A, Ciccocioppo R, Mechirova E, Kruzliak P. The effect of Betanin parenteral pretreatment on Jejunal and pulmonary tissue histological architecture and inflammatory response after Jejunal ischemia-reperfusion injury. Exp Mol Pathol 2019; 110:104292. [PMID: 31377235 DOI: 10.1016/j.yexmp.2019.104292] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 07/10/2019] [Accepted: 07/31/2019] [Indexed: 02/07/2023]
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Zhang M, Li M, Wang R, Qian Y. Effects of acute ammonia toxicity on oxidative stress, immune response and apoptosis of juvenile yellow catfish Pelteobagrus fulvidraco and the mitigation of exogenous taurine. FISH & SHELLFISH IMMUNOLOGY 2018; 79:313-320. [PMID: 29802884 DOI: 10.1016/j.fsi.2018.05.036] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 05/15/2018] [Accepted: 05/22/2018] [Indexed: 06/08/2023]
Abstract
Ammonia can easily form in intensive culture systems due to ammonification of uneaten food and animal excretion, which usually brings detrimental health effects to fish. However, little information is available on the mechanisms of the detrimental effects of ammonia stress and mitigate means in fish. In this study, the four experimental groups were carried out to test the response of yellow catfish to ammonia toxicity and their mitigation through taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. The results showed that ammonia poisoning could induce ammonia, glutamine, glutamate and malondialdehyde accumulation, and subsequently lead to blood deterioration (red blood cell, hemoglobin and serum biochemical index reduced), oxidative stress (superoxide dismutase and catalase activities declined) and immunosuppression (lysozyme, 50% hemolytic complement, total immunoglobulin, phagocytic index and respiratory burst reduced), but the exogenous taurine could mitigate the adverse effect of ammonia poisoning. In addition, ammonia poisoning could induce up-regulation of antioxidant enzymes (Cu/Zn-SOD, CAT, GPx and GR), inflammatory cytokines (TNF, IL-1 and IL-8) and apoptosis (p53, Bax, caspase 3 and caspase 9) genes transcription, suggesting that cell apoptotic and inflammation may relate to oxidative stress. This result will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in fish.
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Affiliation(s)
- Muzi Zhang
- School of Marine Sciences, Ningbo University, Ningbo, 315211, China
| | - Ming Li
- School of Marine Sciences, Ningbo University, Ningbo, 315211, China.
| | - Rixin Wang
- School of Marine Sciences, Ningbo University, Ningbo, 315211, China
| | - Yunxia Qian
- School of Marine Sciences, Ningbo University, Ningbo, 315211, China.
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Okada M, Falcão LFR, Ferez D, Martins JL, Errante PR, Rodrigues FSM, Caricati-Neto A, Marinho M, Fenelon G, Oliveira-Júnior IS. Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion. Acta Cir Bras 2017; 32:964-972. [PMID: 29236801 DOI: 10.1590/s0102-865020170110000008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Accepted: 10/22/2017] [Indexed: 01/23/2023] Open
Abstract
PURPOSE To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. METHODS Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. RESULTS The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. CONCLUSION Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.
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Affiliation(s)
- Mieko Okada
- Fellow PhD degree, Postgraduate Program in Translational Medicine, Universidade Federal de São Paulo (UNIFESP), Brazil. Acquisition, analysis and interpretation of data; technical procedures; statistical analysis, manuscript writing
| | - Luiz Fernando Reis Falcão
- PhD, Associate Professor, Division of Anesthesia, Pain and Intensive Medicine, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Interpretation of data, statistical analysis, manuscript writing, critical revision
| | - David Ferez
- PhD, Associate Professor, Division of Anesthesia, Pain and Intensive Medicine, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Interpretation of data, critical revision
| | - José Luiz Martins
- PhD, Full Professor, Division of Anesthesia, Pain and Intensive Medicine, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Interpretation of data, manuscript writing, critical revision
| | - Paolo Ruggero Errante
- Fellow PhD degree, Postgraduate Program in Pharmacology, UNIFESP, Sao Paulo-SP, Brazil. Histopathological examinations, analysis of data
| | - Francisco Sandro Menezes Rodrigues
- Fellow PhD degree, Postgraduate Program in Pharmacology, UNIFESP, Sao Paulo-SP, Brazil. Histopathological examinations, analysis of data
| | - Afonso Caricati-Neto
- PhD, Associate Professor, Department of Pharmacology, UNIFESP, Sao Paulo-SP, Brazil. Manuscript writing, critical revision
| | - Márcia Marinho
- PhD, Full Professor, Veterinary Medicine School, UNESP, Araçatuba-SP, Brazil. Biochemistry data analysis, statistical analysis, critical revision
| | - Guilherme Fenelon
- Associate Professor, Division of Cardiology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study, manuscript writing, critical revision
| | - Itamar Souza Oliveira-Júnior
- Full Professor, Division of Anesthesia, Pain and Intensive Medicine, Department of Surgery, and Associate Professor, Postgraduate Program in Translational Medicine, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study, critical revision, final approval of the version to be published
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El-Sayyad SM, Soubh AA, Awad AS, El-Abhar HS. Mangiferin protects against intestinal ischemia/reperfusion-induced liver injury: Involvement of PPAR-γ, GSK-3β and Wnt/β-catenin pathway. Eur J Pharmacol 2017; 809:80-86. [PMID: 28506911 DOI: 10.1016/j.ejphar.2017.05.021] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 05/05/2017] [Accepted: 05/10/2017] [Indexed: 12/13/2022]
Abstract
AIM Mangiferin (MF), a xanthonoid from Mangifera indica, possesses anti-inflammatory, immunomodulatory, and potent antioxidant effects; however, its protective effect against mesenteric ischemia/reperfusion (I/R)-induced liver injury has not been fully clarified. The study was designed to assess the possible mechanism of action of MF against mesenteric I/R model. MAIN METHODS Male Wister rats were treated with MF (20mg/kg, i.p) or the vehicle for 3 days before I/R, which was induced by clamping the superior mesenteric artery for 30min followed by declamping for 60min. KEY FINDINGS The mechanistic studies revealed that MF protected the 2 organs studied, viz., liver and intestine partly via increasing the content of β-catenin and PPAR-γ along with decreasing that of GSK-3β and the phosphorylated NF-қB-p65. MF antioxidant effect was evidenced by increasing contents of total antioxidant capacity and GST, besides normalizing that of MDA. Regarding the anti-inflammatory effect, MF reduced IL-1β and IL-6, effects that were mirrored on the tissue content of MPO. Moreover, MF possessed anti-apoptotic character evidenced by elevating Bcl-2 content and reducing that of caspase-3. In the serum, intestinal I/R increased the activity of ALT, AST, and creatine kinase. SIGNIFICANCE The intimated protective mechanisms of MF against mesenteric I/R are mediated, partially, by modulation of oxidative stress, inflammation, and apoptosis possibly via the involvement of Wnt/β-catenin/NF-қβ/ PPAR-γ signaling pathways.
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Affiliation(s)
- Shorouk M El-Sayyad
- Department of Pharmacology & Toxicology, October 6 University,12585 Giza, Egypt
| | - Ayman A Soubh
- Department of Pharmacology & Toxicology, Ahram Canadian University, 12566 Giza, Egypt.
| | - Azza S Awad
- Department of Pharmacology & Toxicology, Ahram Canadian University, 12566 Giza, Egypt
| | - Hanan S El-Abhar
- Department of Pharmacology & Toxicology, Cairo University, 11562 Cairo, Egypt
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12
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Brencher L, Verhaegh R, Kirsch M. Attenuation of intestinal ischemia-reperfusion-injury by β-alanine: a potentially glycine-receptor mediated effect. J Surg Res 2016; 211:233-241. [PMID: 28501123 DOI: 10.1016/j.jss.2016.12.023] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 12/05/2016] [Accepted: 12/21/2016] [Indexed: 11/15/2022]
Abstract
BACKGROUND Acute mesenteric ischemia is often caused by embolization of the mesenteric arterial circulation. Coherent intestinal injury due to ischemia and following reperfusion get visible on macroscopic and histologic level. In previous studies, application of glycine caused an ameliorated intestinal damage after ischemia-reperfusion in rats. Because we speculated that glycine acted here as a signal molecule, we investigated whether the glycine-receptor agonist β-alanine evokes the same beneficial effect in intestinal ischemia-reperfusion. MATERIALS AND METHODS β-alanine (10, 30, and 100 mg/kg) was administered intravenously. Ischemia/reperfusion of the small intestine was initiated by occluding and reopening the superior mesenteric artery in rats. After 90 min of ischemia and 120 min of reperfusion, the intestine was analyzed with regard to macroscopic and histologic tissue damage, the activity of the saccharase, and accumulation of macrophages. In addition, systemic parameters and metabolic ones (e.g., acid-base balance, electrolytes, and blood glucose) were measured at certain points in time. RESULTS All three dosages of β-alanine did not change systemic parameters but prevent from hyponatremia during the period of reperfusion. Most importantly, application of 100-mg β-alanine clearly diminished intestinal tissue damage, getting visible on macroscopic and histologic level. In addition, I/R-mediated decrease of saccharase activity and accumulation of macrophages in the small intestine were ameliorated. CONCLUSIONS The present study demonstrated that β-alanine was a potent agent to ameliorate I/R-induced injury of the small intestine. Due to its diminishing effect on the accumulation of macrophages, β-alanine is strongly expected to mediate its beneficial effect via glycine receptors.
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Affiliation(s)
- Lisa Brencher
- Institut für Physiologische Chemie, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany
| | - Rabea Verhaegh
- Institut für Physiologische Chemie, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
| | - Michael Kirsch
- Institut für Physiologische Chemie, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany
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Ren Q, Li M, Yuan L, Song M, Xing X, Shi G, Meng F, Wang R. Acute ammonia toxicity in crucian carp Carassius auratus and effects of taurine on hyperammonemia. Comp Biochem Physiol C Toxicol Pharmacol 2016; 190:9-14. [PMID: 27510860 DOI: 10.1016/j.cbpc.2016.08.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 07/28/2016] [Accepted: 08/02/2016] [Indexed: 12/18/2022]
Abstract
The four experimental groups were carried out to test the response of crucian carp Carassius auratus to ammonia toxicity and taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected with taurine. Fish in group 2 had the highest ammonia and glutamine contents, and the lowest glutamate content in liver and brain. Serum superoxide dismutase (SOD), glutathione (GSH) activities, red cell count (RBC), white cell count (WBC), lysozyme (LYZ) activity, complement C3 content of fish in group 2 reflected the lowest, but malondialdehyde content was the highest. Importantly, serum SOD and GSH activites, RBC, WBC, and LYZ activity, C3, C4 and total immunoglobulin contents of fish in group 3 were significantly higher than those of fish in group 2. This study indicates that ammonia exerts its toxic effects by interfering with amino acid transport, inducing ROS generation, leading to malondialdehyde accumulation and immunosuppression of crucian carp. The exogenous taurine could mitigate the adverse effect of high ammonia level on fish physiological disorder.
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Affiliation(s)
- Qianyan Ren
- School of Marine Sciences, Ningbo University, Ningbo 315211, China; College of Marine Science, Zhejiang Ocean University, Zhoushan 316000, China
| | - Ming Li
- School of Marine Sciences, Ningbo University, Ningbo 315211, China.
| | - Lixia Yuan
- School of Marine Sciences, Ningbo University, Ningbo 315211, China
| | - Meize Song
- College of Marine Science, Zhejiang Ocean University, Zhoushan 316000, China
| | - Xiaodan Xing
- College of Marine Science, Zhejiang Ocean University, Zhoushan 316000, China
| | - Ge Shi
- College of Marine Science, Zhejiang Ocean University, Zhoushan 316000, China
| | - Fanxing Meng
- School of Marine Sciences, Ningbo University, Ningbo 315211, China
| | - Rixin Wang
- School of Marine Sciences, Ningbo University, Ningbo 315211, China.
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Sukhotnik I, Aranovich I, Ben Shahar Y, Bitterman N, Pollak Y, Berkowitz D, Chepurov D, Coran AG, Bitterman A. Effect of taurine on intestinal recovery following intestinal ischemia-reperfusion injury in a rat. Pediatr Surg Int 2016; 32:161-8. [PMID: 26503339 DOI: 10.1007/s00383-015-3828-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2015] [Indexed: 12/01/2022]
Abstract
PURPOSE Taurine (TAU) is a sulfur-containing amino acid that is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. Several studies have established that treatment with TAU significantly protects cerebral, cardiac and testicular injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of TAU on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats that underwent laparotomy, (2) Sham-TAU rats that underwent laparotomy and were treated with intraperitoneal (IP) TAU (250 mg/kg); (3) IR-rats that underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (4) IR-TAU rats that underwent IR and were treated with IP TAU (250 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK and caspase-3 in the intestinal mucosa was determined using Western blot and immunohistochemistry. RESULTS Treatment with TAU resulted in a significant decrease in Park's injury score compared to IR animals. IR-TAU rats also demonstrated a significant increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum and crypt depth in ileum compared to IR animals. IR-TAU rats also experienced significantly lower apoptotic indices in jejunum and ileum which was accompanied by a higher Bcl-2/Bax ratio compared to IR animals. CONCLUSIONS Treatment with taurine prevents gut mucosal damage and inhibits intestinal epithelial cell apoptosis following intestinal IR in a rat.
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Affiliation(s)
- I Sukhotnik
- Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
- Department of Pediatric Surgery, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, Haifa, 31048, Israel.
| | - I Aranovich
- Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Department of Pediatric Surgery, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, Haifa, 31048, Israel
| | - Y Ben Shahar
- Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Department of Surgery, Carmel Medical Center, Haifa, Israel
| | - N Bitterman
- Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Y Pollak
- Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - D Berkowitz
- Department of Gastroenterology, Bnai Zion Medical Center, Haifa, Israel
| | - D Chepurov
- Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - A G Coran
- Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI, USA
| | - A Bitterman
- Department of Surgery, Carmel Medical Center, Haifa, Israel
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Maretta M, Tóth Š, Jonecová Z, Veselá J. Impact of alanyl-glutamine dipeptide on proliferative and inflammatory changes in jejunal mucosa after acute mesenteric ischemia. J Pediatr Surg 2014; 49:1385-9. [PMID: 25148743 DOI: 10.1016/j.jpedsurg.2014.01.056] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Revised: 12/09/2013] [Accepted: 01/03/2014] [Indexed: 02/02/2023]
Abstract
PURPOSE The aim of our study was to determinate the impact of dipeptide (alanyl-glutamine) administration on inflammatory and proliferative changes in jejunal mucosa after acute mesenteric ischemia. METHODS Male Wistar rats (n=30) were divided into three groups: ischemia/reperfusion (IR) group which undergoes 60min of mesenteric ischemia and 1 or 24h of reperfusion (IR1, IR24, n=12). Groups with dipeptide administration (D+IR1, D+IR24, Dipeptiven con inf., i.v., 0.75 g/kg) prior to IR injury were followed by 1 and 24h of reperfusion. At the end of reperfusion period jejunal bioptic samples were obtained for histological (H&E), histochemical (Alcian blue) and immunohistochemical (anti-PCNA, anti-MPO) evaluations. RESULTS Our results pointed out a significant (p<0.001) increase of histopathological injury score in IR1 group compared to D+IR1 group. Immunohistochemical evaluation showed that MPO-positivity was significantly increased in IR groups after 1 (p<0.001) as well as 24h of reperfusion (p<0.01) compared to dipeptide pretreated groups. Proliferative/reparatory rate was assessed using anti-PCNA antibody and showed a significant increase (p<0.01) in PCNA cell positivity in lamina propria in dipeptide treated group compared to IR group. CONCLUSION In conclusion we may suggest that administration of alanyl-glutamine dipeptide prior to IR injury may help to protect small intestine and its mucous membrane integrity against insult such as intestinal ischemic/reperfusion injury presents.
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Affiliation(s)
- Milan Maretta
- Department of Histology and Embryology, Faculty of Medicine, Pavol Jozef Šafárik University, Šrobárova 2, Košice, Slovak Republic.
| | - Štefan Tóth
- Department of Histology and Embryology, Faculty of Medicine, Pavol Jozef Šafárik University, Šrobárova 2, Košice, Slovak Republic
| | - Zuzana Jonecová
- Department of Histology and Embryology, Faculty of Medicine, Pavol Jozef Šafárik University, Šrobárova 2, Košice, Slovak Republic
| | - Jarmila Veselá
- Department of Histology and Embryology, Faculty of Medicine, Pavol Jozef Šafárik University, Šrobárova 2, Košice, Slovak Republic
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Ozacmak HS, Ozacmak VH, Barut F, Araslı M, Ucan BH. Pretreatment with mineralocorticoid receptor blocker reduces intestinal injury induced by ischemia and reperfusion: involvement of inhibition of inflammatory response, oxidative stress, nuclear factor κB, and inducible nitric oxide synthase. J Surg Res 2014; 191:350-61. [PMID: 24862878 DOI: 10.1016/j.jss.2014.04.040] [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: 01/02/2014] [Revised: 04/20/2014] [Accepted: 04/24/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Spironolactone (Sp), a mineralocorticoid receptor antagonist, protects against the ischemia reperfusion (IR) injury of retina, kidney, heart, and brain. We aimed to investigate the effects of Sp on intestinal IR injury. METHODS Male Wistar rats were randomly divided into: (1) a sham control group; (2) an IR control group, subjected to 30 min ischemia and 3 h reperfusion; (3) a group treated with Sp (20 mg/kg) for 3 d before the IR; and (4) a sham-operated control group treated with Sp (20 mg/kg). After the reperfusion, blood and intestinal tissue samples were collected to evaluate histopathologic state, neutrophil infiltration (by measuring myeloperoxidase activity), levels of the cytokines (tumor necrosis factor α, interleukin 1α [IL-1α], interferon γ, monocyte chemotactic protein-1, granulocyte macrophage-colony stimulating factor, and IL-4), malondialdehyde (MDA) and reduced glutathione contents, and immunohistochemical expressions of nuclear factor κB, inducible nitric oxide synthase (iNOS), and caspase-3. RESULTS MDA content, myeloperoxidase activity, and plasma levels of tumor necrosis factor α, IL-1α, and monocyte chemotactic protein-1 were all elevated in IR, indicating the oxidative stress and local and systemic inflammatory response. Sp administration markedly reduced the MDA content and the cytokine levels. The pretreatment alleviated intestinal injury, neutrophil infiltration, and the expressions of caspase-3, iNOS, and NFκB. CONCLUSIONS The results implicate that Sp may have a strong protective effect against the intestinal IR injury. The effect can be mediated via suppression of both systemic inflammatory response and apoptosis through amelioration of oxidative stress and generation of proinflammatory cytokines, iNOS, caspase-3, and nuclear factor κB. Therefore, mineralocorticoid receptor antagonism might be of potential therapeutic benefit in cases of intestinal IR damage.
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Affiliation(s)
- Hale Sayan Ozacmak
- Department of Physiology, Bülent Ecevit University Medical School, Zonguldak, Turkey
| | - Veysel Haktan Ozacmak
- Department of Physiology, Bülent Ecevit University Medical School, Zonguldak, Turkey.
| | - Figen Barut
- Department of Medical Pathology, Bülent Ecevit University Medical School, Zonguldak, Turkey
| | - Mehmet Araslı
- Department of Immunology, Bülent Ecevit University Medical School, Zonguldak, Turkey
| | - Bulent Hamdi Ucan
- Department of General Surgery, Bülent Ecevit University Medical School, Zonguldak, Turkey
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17
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Okudan N, Belviranlı M, Gökbel H, Oz M, Kumak A. Protective effects of curcumin supplementation on intestinal ischemia reperfusion injury. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2013; 20:844-848. [PMID: 23647746 DOI: 10.1016/j.phymed.2013.03.022] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Revised: 02/08/2013] [Accepted: 03/27/2013] [Indexed: 06/02/2023]
Abstract
The aim of this study was to investigate the effects curcumin on inflammation and oxidative stress markers in the intestinal ischemia reperfusion (IIR) injury induced rats. Rats were divided into four groups: sham (S), intestinal IR (IIR), curcumin plus sham (CS), and curcumin plus intestinal IR (CIIR). Curcumin was given 200 mg kg⁻¹ for 20 days. IIR was produced by 45 min of intestinal ischemia followed by a 120 min of reperfusion. Although interleukin-6 levels tended to increase in IIR group tumor necrosis factor-α levels were not different. Intestinal myeloperoxidase activity in CS group was lower than IIR group. In intestine and heart tissues, malondialdehyde levels in CS and CIIR groups were lower than S and IIR groups. Superoxide dismutase activity in CIIR group was higher than IIR group in intestine and lung tissues. Curcumin has a protective role against ischemia reperfusion injury.
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Affiliation(s)
- N Okudan
- Department of Physiology, Faculty of Medicine, Selçuk University, Konya, Turkey
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Xiang L, Tan JW, Huang LJ, Jia L, Liu YQ, Zhao YQ, Wang K, Dong JH. Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine. World J Gastroenterol 2012; 18:5197-204. [PMID: 23066313 PMCID: PMC3468851 DOI: 10.3748/wjg.v18.i37.5197] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2012] [Revised: 06/18/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of H2 gas on liver injury in massive hepatectomy using the Intermittent Pringle maneuver in swine.
METHODS: Male Bama pigs (n = 14) treated with ketamine hydrochloride and Sumianxin II as induction drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups: Hydrogen-group (n = 7), the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; Contrast-group (n = 7), underwent 70% hepatotectomy without inhalation of hydrogen. Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) in liver tissue were measured at pre-operation, post-hepatotectomy (PH) 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine.
RESULTS: There were no significant differences in body weight, blood loss and removal liver weight between the two groups. There was no significant difference in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in Contrast-group at PH 3 h, although there were no significant difference (P = 0.655). ALT and AST in Hydrogen-group was significantly lower comparing to Contrast-group (P = 0.036, P = 0.011, vs P = 0.032, P = 0.013) at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH 1 h and 3 h. In the hydrogen gas treated-group, the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group (P = 0.0005, P = 0.0004). In Hydrogen-group, the HA level was also significantly low to Contrast-group (P = 0.0005, P = 0.0005) although the two groups all increased at PH 1 h and 3 h. The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group. However, PCNA index (%) was not statistically significant between the two groups (P = 0.802). Microphotometric evaluation of apoptotic index (AI) in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h, the AI% level in the hydrogen was significantly low to Contrast-group (P = 0.012). There were no significant difference between Hydrogen-group and Contrast-group at pre-operation (P = 0.653, P = 0.423), but after massive hepatotectomy, the TNF-α and IL-6 levels increase, and its in Hydrogen-group was significantly low compared with Contrast-group (P = 0.022, P = 0.013, vs P = 0.016, P = 0.012), respectively. Hydrogen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis.
CONCLUSION: H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy, possibly by the reduction of inflammation and oxidative stress, maybe a potential agent for treatment in clinic.
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Zhang T, Wang Y, Ban R, Tong L, Qiao H, Lao H, Zhao H, Jiang X, Sun X, Zhang F. Oral administration of lactoferrin attenuates intestinal ischemia-reperfusion injury in rats. ACTA ACUST UNITED AC 2012; 49:99-106. [PMID: 23051927 DOI: 10.1159/000342633] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2012] [Accepted: 08/12/2012] [Indexed: 01/10/2023]
Abstract
BACKGROUND Intestinal ischemia-reperfusion (I/R) is a common and serious clinical condition. Lactoferrin (Lf) has displayed antioxidative and anti-inflammatory activities in protecting the intestinal mucosa. The objective of this study was to investigate whether oral administration of Lf could attenuate I/R-induced intestinal injury. METHODS The experimental design consisted of three groups of Wistar rats (24 per group): sham operation, control (I/R, saline), Lf (I/R, Lf). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 45 min. Eight rats from each group were randomly sacrificed 3, 12 or 36 h after reperfusion, and blood and intestinal samples were collected. RESULTS Intestinal I/R resulted in gut damage evidenced by morphological alteration, reduction of γ-glutamyl transpeptidase (γ-GGT) activity and increased cell apoptosis. Daily administration of Lf (200 mg/kg) for 14 days before surgery significantly attenuated gut damage by reducing the histologic score and apoptosis index, and restoring intestinal γ-GGT activity. Lf reduced intestinal malondialdehyde and myeloperoxidase, restored glutathione and decreased serum levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 compared with saline control in I/R rats. In addition, oral administration of Lf did not produce any significant effects in healthy rats; Lf at doses of 50 or 100 mg/kg also attenuated I/R-induced gut damage, but administration of Lf for 7 days did not exert a significant protective effect against I/R-induced gut damage. CONCLUSIONS These results indicate that Lf may serve as a potent supplement in protecting the gut from intestinal I/R-induced injury by its antioxidative, anti-inflammatory and antiapoptotic activities.
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Affiliation(s)
- T Zhang
- Department of Surgery, Fifth Affiliated Hospital of Harbin Medical University, Daqing, China
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20
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Ginsenoside Rb1 attenuates intestinal ischemia reperfusion induced renal injury by activating Nrf2/ARE pathway. Molecules 2012; 17:7195-205. [PMID: 22692243 PMCID: PMC6268105 DOI: 10.3390/molecules17067195] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Revised: 06/04/2012] [Accepted: 06/05/2012] [Indexed: 01/27/2023] Open
Abstract
Intestinal ischemia reperfusion (IIR) is a serious clinical condition associated with simultaneous multiple organ dysfunction. The aim of this study was to investigate the effects of ginsenoside Rb1 on IIR induced renal injury in mice. An intestinal ischemia reperfusion mouse model was established by superior mesenteric artery (SMA) occlusion for 45 min, followed by reperfusion for 2 h. IIR induced renal injury characterized by increase of BUN, Cr and NGAL in serum, MDA levels and decrease of SOD levels in the renal tissues. Ginsenoside Rb1 (30, 60 mg/kg) given intraperitoneally before reperfusion attennuated renal injury, which was associated with decrease of BUN, Cr and NGAL in serum, MDA levels and increase of SOD levels in the renal tissues. Furthermore, the immunohistochemistry and Western blot data showed that ginsenoside Rb1 dramatically reversed IIR induced renal injury, associated with upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in renal tissues. Our data suggests that ginsenoside Rb1 attenuates acute renal injury induced by intestinal ischemia reperfusion by activating the Nrf2/ARE pathway.
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Wang D, Ma Y, Li Z, Kang K, Sun X, Pan S, Wang J, Pan H, Liu L, Liang D, Jiang H. The role of AKT1 and autophagy in the protective effect of hydrogen sulphide against hepatic ischemia/reperfusion injury in mice. Autophagy 2012; 8:954-62. [PMID: 22694815 DOI: 10.4161/auto.19927] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Hydrogen sulphide (H 2S) exerts a protective effect in hepatic ischemia-reperfusion (I/R) injury. However, the exact mechanism of H 2S action remains largely unknown. This study was designed to investigate the role of the PtdIns3K-AKT1 pathways and autophagy in the protective effect of H 2S against hepatic I/R injury. Primary cultured mouse hepatocytes and livers with or without NaHS (a donor of H 2S) preconditioning were exposed to anoxia/reoxygenation (A/R) and I/R, respectively. In certain groups, they were also pretreated with LY294002 (AKT1-specific inhibitor), 3-methyladenine (3MA, autophagy inhibitor) or rapamycin (autophagy enhancer), alone or simultaneously. Cell viability, expression of P-AKT1, T-AKT1, LC3 and BECN1 were examined. The severity of liver injury was measured by the levels of serum aminotransferase and inflammatory cytokine, apoptosis and histological examination. GFP-LC3 redistribution and transmission electron microscopy were used to test the activity of autophagy. H 2S preconditioning activated PtdIns3K-AKT1 signaling in hepatocytes. LY294002 could abolish the AKT1 activation and attenuate the protective effect of H 2S on hepatocytes A/R and hepatic I/R injuries. H 2S suppressed hepatic autophagy in vitro and in vivo. Further reducing autophagy by 3MA also diminished the protective effect of H 2S, while rapamycin could reverse the autophagy inhibitory effect and enhance the protective effect of H 2S against hepatocytes A/R and hepatic I/R injuries, consequently. Taken together, H 2S protects against hepatocytic A/R and hepatic I/R injuries, at least in part, through AKT1 activation but not autophagy. An autophagy agonist could be applied to potentiate this hepatoprotective effect by reversing the autophagy inhibition of H 2S.
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Affiliation(s)
- Dawei Wang
- Key Laboratory of Hepatosplenic Surgery, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China
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Christophersen OA. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2012; 23:14787. [PMID: 23990836 PMCID: PMC3747764 DOI: 10.3402/mehd.v23i0.14787] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Accepted: 11/18/2011] [Indexed: 12/28/2022]
Abstract
There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs), but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: (1) during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, (2) after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, (3) by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various damaged tissues, especially in the intestines, and (4) by functioning as an antifibrogenic agent. A detailed discussion is given of possible mechanisms involved both in the antioxidant effects of taurine, in its anti-inflammatory effects and in its role as a growth factor for leukocytes and nerve cells, which might be closely related to its role as an osmolyte important for cellular volume regulation because of the close connection between cell volume regulation and the regulation of protein synthesis as well as cellular protein degradation. While taurine supplementation alone would be expected to exert a therapeutic effect far better than negligible in patients that have been exposed to high doses of ionizing radiation, it may on theoretical grounds be expected that much better results may be obtained by using taurine as part of a multifactorial treatment strategy, where it may interact synergistically with several other nutrients, hormones or other drugs for optimizing antioxidant protection and minimizing harmful posttraumatic inflammatory reactions, while using other nutrients to optimize DNA and tissue repair processes, and using a combination of good diet, immunostimulatory hormones and perhaps other nontoxic immunostimulants (such as beta-glucans) for optimizing the recovery of antiviral and antibacterial immune functions. Similar multifactorial treatment strategies may presumably be helpful in several other disease situations (including severe infectious diseases and severe asthma) as well as for treatment of acute intoxications or acute injuries (both mechanical ones and severe burns) where severely enhanced oxidative and/or nitrative stress and/or too much secretion of vasodilatory neuropeptides from C-fibres are important parts of the pathogenetic mechanisms that may lead to the death of the patient. Some case histories (with discussion of some of those mechanisms that may have been responsible for the observed therapeutic outcome) are given for illustration of the likely validity of these concepts and their relevance both for treatment of severe infections and non-infectious inflammatory diseases such as asthma and rheumatoid arthritis.
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Zhang F, Wang X, Tong L, Qiao H, Li X, You L, Jiang H, Sun X. Matrine attenuates endotoxin-induced acute liver injury after hepatic ischemia/reperfusion in rats. Surg Today 2011; 41:1075-84. [PMID: 21773896 DOI: 10.1007/s00595-010-4423-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2009] [Accepted: 08/16/2010] [Indexed: 01/09/2023]
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Petrat F, Rönn T, de Groot H. Protection by Pyruvate Infusion in a Rat Model of Severe Intestinal Ischemia-Reperfusion Injury. J Surg Res 2011; 167:e93-e101. [DOI: 10.1016/j.jss.2009.12.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2009] [Revised: 11/03/2009] [Accepted: 12/08/2009] [Indexed: 11/30/2022]
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Hydrogen sulfide attenuates ischemia-reperfusion injury in in vitro and in vivo models of intestine free tissue transfer. Plast Reconstr Surg 2010; 125:1670-1678. [PMID: 20517090 DOI: 10.1097/prs.0b013e3181d4fdc5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Ischemia-reperfusion injury is the propagation of injury following reintroduction of oxygen to previously ischemic tissue. The purpose of this study was to evaluate whether hydrogen sulfide provides protection against ischemia-reperfusion injury in enteric tissue. METHODS In vitro (enterocyte anoxia-normoxia) and in vivo (rat intestinal ischemia-reperfusion) models of ischemia-reperfusion injury were tested with or without the addition of hydrogen sulfide. Apoptotic index was determined in vitro, and gross appearance, histology, and villus height (a measure of mucosal integrity) were assessed in vivo. Statistical analysis was performed, and significance was defined as p < 0.05. RESULTS In vitro, cells treated with 10 microM hydrogen sulfide after 1-hour anoxia experienced a significant decrease in apoptotic index compared with untreated control (0.5 +/- 0.3 percent versus 2.8 +/- 0.7 percent); after 3 hours of anoxia, cells treated with 1 microM, 10 microM, and 100 microM hydrogen sulfide experienced significant decreases in apoptotic index versus untreated control (1.6 +/- 0.8 percent, 1.8 +/- 0.9 percent, and 2.8 +/- 0.7 percent versus 8.6 +/- 1.7 percent). In vivo, intestine treated with [10 microM] or [100 microM] hydrogen sulfide retained normal coloration and villus architecture after 1-hour ischemia; after 2 hours of ischemia, only intestine treated with [10 microM] hydrogen sulfide appeared uninjured. After 1, 2, or 3 hours of ischemia, villus heights of intestine treated with [10 microM] or [100 microM] hydrogen sulfide were significantly higher than heights of non-hydrogen sulfide-treated villi. CONCLUSIONS Hydrogen sulfide significantly attenuates ischemia-reperfusion injury in intestinal tissue in vitro and in vivo. These results have significant implications for enteric free tissue transfers and other gastrointestinal procedures in which ischemic intervals may be anticipated.
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Delić D, Warskulat U, Borsch E, Al-Qahtani S, Al-Quraishi S, Häussinger D, Wunderlich F. Loss of ability to self-heal malaria upon taurine transporter deletion. Infect Immun 2010; 78:1642-9. [PMID: 20100858 PMCID: PMC2849432 DOI: 10.1128/iai.01159-09] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2009] [Revised: 11/24/2009] [Accepted: 01/18/2010] [Indexed: 12/31/2022] Open
Abstract
Deletion of the taurine transporter gene (taut) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show that taut-/- mice have lost their ability to self-heal blood-stage infections with Plasmodium chabaudi malaria. All taut-/- mice succumb to infections during crisis, while about 90% of the control taut(+/+) mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion of taut, however, results in the lowering of circulating taurine levels from 540 to 264 micromol/liter, and infections cause additional lowering to 192 micromol/liter. Peak parasitemia levels in taut-/- mice are approximately 60% higher than those in taut(+/+) mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels, as well as with liver injuries. The latter manifest as increased systemic ammonia levels, a perturbed capacity to entrap injected particles, and increased expression of genes encoding TNF-alpha, IL-1beta, IL-6, inducible nitric oxide synthase (iNOS), NF-kappaB, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infected taut-/- mice. Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency due to taut deletion, however, impairs the eryptosis of P. chabaudi-parasitized erythrocytes and expedites increases in systemic TNF-alpha, IL-1beta, and ammonia levels, presumably contributing to multiorgan failure in P. chabaudi-infected taut-/- mice.
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Affiliation(s)
- Denis Delić
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
| | - Ulrich Warskulat
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
| | - Elena Borsch
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
| | - Saad Al-Qahtani
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
| | - Saleh Al-Quraishi
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
| | - Dieter Häussinger
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
| | - Frank Wunderlich
- Division of Molecular Parasitology, Department of Biology, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine- University, Universitätsstr. 1, Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany, Teacher College, Zoology Department, College of Science, King Saud University, 11352 Riyadh, Saudi Arabia
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Kang K, Zhao M, Jiang H, Tan G, Pan S, Sun X. Role of hydrogen sulfide in hepatic ischemia-reperfusion-induced injury in rats. Liver Transpl 2009; 15:1306-14. [PMID: 19790158 DOI: 10.1002/lt.21810] [Citation(s) in RCA: 107] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Hydrogen sulfide (H2S) displays anti-inflammatory and cytoprotective activities as evidenced by the inhibition of myocardial ischemia-reperfusion injury and production of lipid peroxidation. H2S also exerts many physiological or pathological effects on livers. Therefore, we designed the present study to investigate the roles of H2S in hepatic ischemia-reperfusion (HIR)-induced injury in rats by measuring H2S levels, H2S synthesizing activity, and cystathionine gamma-lyase (CSE) messenger RNA (mRNA) expression. We also applied DL-propargyl glycine (PAG) and sodium hydrosulfide (NaHS) to investigate their effects on the severity of liver injury induced by HIR. The levels of H2S, H2S production activity, and CSE mRNA expression in livers were increased by HIR. Administration of NaHS significantly attenuated the severity of liver injury and inhibited the production of lipid peroxidation, serum inflammatory factors [including nitric oxide, tumor necrosis factor alpha (TNF-alpha), interleukin 10, and intercellular cell adhesion molecule 1], cell apoptosis, and apoptosis-related proteins (including caspase-3, Fas, Fas ligand, and TNF-alpha), which were caused or elevated by HIR, whereas PAG aggravated them. However, NaHS or PAG did not show significant effects on the activation of caspase-9, which was also increased by HIR. Although further investigation is required, this study may indicate that H2S plays a protective role in HIR-induced injury.
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Affiliation(s)
- Kai Kang
- Hepatosplenic Surgery Center, Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
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Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Alarcón-Galván G, Cordero-Pérez P, Fernández-Garza NE. The effects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury in rats. Eur J Pharmacol 2009; 621:78-85. [PMID: 19751722 DOI: 10.1016/j.ejphar.2009.08.038] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2009] [Revised: 08/14/2009] [Accepted: 08/20/2009] [Indexed: 11/26/2022]
Abstract
Intestinal ischemia/reperfusion causes severe injury and alters motility. N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to reduce ischemia/reperfusion injury in the nervous system, and in other organs. In this study, we set out to investigate the effects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury. Male Wistar rats were randomly divided into four groups: (1) a control, sham-operated group; (2) an intestinal ischemia/reperfusion group subjected to 45 min ischemia and 1h reperfusion; (3) a group treated with 10 mg/kg ketamine before ischemia/reperfusion; and (4) a group treated with 10 mg/kg memantine before ischemia/reperfusion. Intestinal samples were taken for histological evaluation. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capacity, tumor necrosis factor alpha (TNF-alpha), P-selectin and antithrombin III (ATIII) were measured. Intestinal transit time was determined to evaluate intestinal motility. Fecal pellet output and animal weight were also registered daily for 7 days post-ischemia. After reperfusion, AST, LDH, TNF-alpha and P-selectin levels were elevated, ATIII levels were depleted, and ALT levels were unchanged in serum. Additionally, levels of MDA were increased and total antioxidant capacity was reduced in serum, indicating oxidative stress. Intestinal mucosa showed severe injury. Ketamine, but not memantine, diminished these alterations. Intestinal motility and fecal pellet output were also altered after ischemia/reperfusion. Both drugs abolished the alterations in motility. In conclusion, ketamine's protective effects over ischemia/reperfusion do not appear to be NMDA mediated, but they could be playing a role in protecting the intestine against ischemia-induced functional changes.
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Deng ZY, Guo GH, Yang Y. Effects of early enteral glutamine supplementation on tight junctions in intestinal mucosa of scalded rats. Shijie Huaren Xiaohua Zazhi 2009; 17:2031-2036. [DOI: 10.11569/wcjd.v17.i20.2031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the protective effects of early enteral glutamine supplementation on the barrier function of intestinal mucosa in scalded rats and explore the mechanism underlying such protective effects.
METHODS: Healthy adult SD rats were subjected to a 30% TBSA third-degree scald injury to develop a rat model of scald injury. Scalded rats were then randomly divided into EN and EN plus Gln group, respectively. Rats in the EN group were fed standard enteral nutrition (Nutrison Multi Fibre) while those in the EN plus Gln group were fed standard enteral nutrition plus Gln. On days 1, 4, 7 and 10 after scald induction, plasma D-lactic acid levels were analyzed by ultraviolet spectrophotometry, the expression of Occludin protein was detected by Western blot, and the expression of ZO-1 mRNA was determined by RT-PCR.
RESULTS: Serum D-lactic acid level was elevated in response to scald induction. The levels of D-lactic acid in the serum of rats in the EN group did not return to normal within the period of observation of this study, whereas those in the EN plus Gln group returned to normal on day 4 after scald induction (4.5 ± 0.8 mg/L vs 3.8 ± 0.6 mg/L). Semiquantitative Western blot analysis showed that the expression of Occludin protein in intestinal mucosa of rats in the EN plus Gln group showed an initial rise, followed by a decline. On days 4 and 7, the expression level of Occludin protein in intestinal mucosa of rats in the EN plus Gln group were significantly higher than those in the EN group (1.18 ± 0.14 vs 0.79 ± 0.09 and 1.59 ± 0.16 vs 1.12 ± 0.13, respectively; both P < 0.05). In both groups, the expression levels of ZO-1 mRNA on day 1 significantly declined when compared with pre-induction values (0.71 ± 0.19 and 0.76 ± 0.17 vs 1.00, both P < 0.05). On day 4, a significant difference was noted in the expression levels of ZO-1 mRNA between the two groups (1.17 ± 0.16 vs 0.76 ± 0.15; P < 0.05) though no significant differences were found at other time points.
CONCLUSION: Early enteral glutamine supplementation is superior to standard enteral nutrition in promoting the expression of Occludin protein and ZO-1 mRNA in intestinal mucosa and improving the barrier function of intestinal mucosa.
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Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. Amino Acids 2009; 38:237-45. [PMID: 19263195 DOI: 10.1007/s00726-009-0233-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2008] [Accepted: 01/05/2009] [Indexed: 12/15/2022]
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Cui W, Wen Y, Dong YL, Liu P. Effect of glutamine on intestinal epithelial barrier permeability in vitro. Shijie Huaren Xiaohua Zazhi 2008; 16:3729-3733. [DOI: 10.11569/wcjd.v16.i33.3729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the mechanism of glutamine (GLN) underlying maintenance of intestinal barrier permeability.
METHODS: Caco-2 cells were placed on Transwell filters and grown in a culture medium composed of DMEM with indicated concentration of GLN (0, 0.1, 1, 4 mmol/L) for 21 d before treatment. Next, transepithelial electrical resistance (TEER) was measured. The localization and expression of tight junction (TJ) protein occludin were measured under immunofluorescence light microscopy. Cells were lysed into detergent-soluble and -insoluble protein fractions and the expression of active or non active occludin protein were measured using Western blot.
RESULTS: Transepithelial electrical resistance was significantly raised following GLN supplementation compared with 0 mmol/L GLN group (21.4 ± 0.1, 124.5 ± 0.3, 173.6 ± 0.2 vs 11.3 ± 0.3, P < 0.05). Immunofluorescence test showed that occludin protein was localized in cytoplasm, with increasing GLN, positive occludin appeared as continuous belt-like structures encircling the cells at the apical cellular junctions in 0 mmol/L GLN group. GLN deprivation did not affect 65-kDa occludin expression, but 85- kDa occludin expression was down-regulated (1.04 ± 0.03, 1.17 ± 0.04, 1.29 ± 0.03, 1.43 ± 0.06, P < 0.05).
CONCLUSION: Deprivation of glutamine decreases active occludin protein expression and increases the intestinal barrier permeability, which is partially reversible with GLN supplementation.
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Zhao J, Yu S, Tong L, Zhang F, Jiang X, Pan S, Jiang H, Sun X. Oxymatrine attenuates intestinal ischemia/reperfusion injury in rats. Surg Today 2008; 38:931-7. [PMID: 18820869 DOI: 10.1007/s00595-008-3785-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2008] [Accepted: 03/16/2008] [Indexed: 12/12/2022]
Abstract
PURPOSE Intestinal ischemia/reperfusion (I/R) is a common and serious clinical condition. The anti-inflammatory and anti-apoptotic properties of oxymatrine, the extract from a traditional Chinese herb, Sophora flavescens Ait, have been shown to protect the liver from I/R injury and attenuate colitis. The objective of this study was to investigate if oxymatrine could attenuate intestinal I/R injury induced in rats. METHODS The experimental design consisted of three groups of 24 Wistar rats each: a sham-operation group (control group), a group subjected to intestinal I/R and then given saline (saline group), and a group subjected to intestinal I/R and then given oxymatrine (oxymatrine group). Intestinal I/R was induced by occluding the superior mesenteric artery for 45 min. Six rats from each group were killed at selected time points, and blood and intestinal samples were collected. RESULTS Morphological alteration, reduction of gamma-glutamyl transpeptidase (gamma-GGT) activity, and increased cell apoptosis confirmed intestinal I/R injury. The oxymatrine group had a significantly lower histological score and apoptosis index than the saline group, demonstrating that the preadministration of oxymatrine attenuated gut damage. Moreover, oxymatrine inhibited the production of lipid peroxides (LPO), decreased the serum levels of tumor necrosis factor (TNF)-alpha, and downregulated expression of phosphorylated p38 mitogen-activated protein kinase, Fas, and FasL, which had been elevated by I/R. CONCLUSIONS These results provide further evidence of the anti-inflammatory and anti-apoptotic activities of oxymatrine, which may become a potent drug for protecting the intestines against I/R injury.
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Affiliation(s)
- Jinpeng Zhao
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
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