{"title":"半胱胺通过增强细胞内硫醇活性减轻肠系膜动脉闭塞引起的肠再灌注损伤。","authors":"Babatunde Alabi, Olugbenga Iwalewa, Temidayo Omobowale, Adeolu Adedapo, Opeyemi Hammed, Richard Ajike, Oladele Afolabi","doi":"10.1055/a-1974-9132","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H<sub>2</sub>O<sub>2</sub>, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H<sub>2</sub>O<sub>2,</sub> MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers.</p><p><strong>Conclusion: </strong>Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 3","pages":"137-145"},"PeriodicalIF":1.7000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Cysteamine Attenuate Intestinal Reperfusion Injury Induced by Occlusion of Mesenteric Artery by Enhancing Intracellular Thiol Activities.\",\"authors\":\"Babatunde Alabi, Olugbenga Iwalewa, Temidayo Omobowale, Adeolu Adedapo, Opeyemi Hammed, Richard Ajike, Oladele Afolabi\",\"doi\":\"10.1055/a-1974-9132\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H<sub>2</sub>O<sub>2</sub>, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H<sub>2</sub>O<sub>2,</sub> MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers.</p><p><strong>Conclusion: </strong>Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.</p>\",\"PeriodicalId\":11451,\"journal\":{\"name\":\"Drug Research\",\"volume\":\"73 3\",\"pages\":\"137-145\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/a-1974-9132\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/a-1974-9132","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Cysteamine Attenuate Intestinal Reperfusion Injury Induced by Occlusion of Mesenteric Artery by Enhancing Intracellular Thiol Activities.
Background: Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H2O2, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H2O2, MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers.
Conclusion: Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.
期刊介绍:
Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.