Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury
| Autor: | Mohamed Ia Hassan, Fares E.M. Ali, Abdel-Gawad S Shalkami |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Adrenergic Antagonists Nitric Oxide Synthase Type III Health Toxicology and Mutagenesis Anti-Inflammatory Agents Nitric Oxide Synthase Type II Inflammation Pharmacology Toxicology 03 medical and health sciences 0302 clinical medicine Enos Male rats medicine Animals Rats Wistar Interleukin 6 Carvedilol Peroxidase biology Interleukin-6 Tumor Necrosis Factor-alpha business.industry Liver Diseases General Medicine medicine.disease biology.organism_classification Hepatic ischemia Toll-Like Receptor 4 Oxidative Stress 030104 developmental biology Liver Cyclooxygenase 2 Reperfusion Injury 030220 oncology & carcinogenesis biology.protein medicine.symptom business Reperfusion injury Signal Transduction medicine.drug |
| Zdroj: | Human & Experimental Toxicology. 40:1362-1373 |
| ISSN: | 1477-0903 0960-3271 |
| DOI: | 10.1177/0960327121999442 |
| Popis: | Aim: Hepatic ischemia/reperfusion (I/R) injury is a syndrome involved in allograft dysfunction. This work aimed to elucidate carvedilol (CAR) role in hepatic I/R injury. Methods: Male rats were allocated to Sham group, CAR group, I/R group and CAR plus I/R group. Rats subjected to hepatic ischemia for 30 minutes then reperfused for 60 minutes. Oxidative stress markers, inflammatory cytokines and nitric oxide synthases were measured in hepatic tissues. Results: Hepatocyte injury following I/R was confirmed by a marked increase in liver enzymes. Also, hepatic I/R increased the contents of malondialdehyde however decreased glutathione contents and activities of antioxidant enzymes. Furthermore, hepatic I/R caused elevation of toll-like receptor-4 (TLR-4) expression and inflammatory mediators levels such as tumor necrosis factor-α, interleukin-6 and cyclooxygenase-II. Hepatic I/R caused down-regulation of endothelial nitric oxide synthase and upregulation of inducible nitric oxide synthase expressions. CAR treatment before hepatic I/R resulted in the restoration of liver enzymes. Administration of CAR caused a significant correction of oxidative stress and inflammation markers as well as modulates the expression of endothelial and inducible nitric oxide synthase. Conclusions: CAR protects liver from I/R injury through reduction of the oxidative stress and inflammation, and modulates endothelial and inducible nitric oxide synthase expressions. |
| Databáze: | OpenAIRE |
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