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Carvedilol protects against hepatic ischemia/reperfusion injury in high-fructose/high-fat diet-fed mice: Role of G protein-coupled receptor kinase 2 and 5
Faculty
Pharmacy
Year:
2019
Type of Publication:
ZU Hosted
Pages:
Authors:
Eslam Ahmed Abdelhamid ebrahiem
Staff Zu Site
Abstract In Staff Site
Journal:
Toxicology and applied pharmacology Science direct
Volume:
Keywords :
Carvedilol protects against hepatic ischemia/reperfusion injury
Abstract:
Hepatic ischemia/reperfusion injury (H-IRI) is associated with irreversible liver damage. The current study aimed to investigate the protective effect of carvedilol against H-IRI in high-fructose high-fat diet (HFrHFD)-fed mice and the role of G protein-coupled receptor kinase 2 and 5 (GRK2 and GRK5). Mice were fed HFrHFD for 16 weeks; then mice were subjected to 30 min of ischemia followed by 1 h of reperfusion at the end of feeding period. Carvedilol (20 mg/kg, i.p.) was administered 30 min before ischemia. To explore the role of GRK2 and GRK5 in mediating carvedilol effects, paroxetine (GRK2 inhibitor, 10 mg/kg, i.p.) and amlexanox (GRK5 inhibitor, 25 mg/kg, i.p.) were administered 30 min before carvedilol administration. Liver function, histopathology and hepatic oxidative stress, as well as inflammatory and apoptotic markers were measured at the end of the experiment. In addition, adrenergic receptor downstream signals were measured in the liver. Results showed increased markers of liver injury (ALT and AST) in mice subjected to H-IRI. Moreover, liver injury was associated with slight collagen deposits as revealed by histopathology and elevated hepatic levels of oxidative stress, inflammatory and apoptotic markers. On the other hand, carvedilol protected mice against H-IRI and improved all associated pathological changes. Furthermore, pre-injection of either GRK2 or GRK5 inhibitor did not change carvedilol effects on serum ALT level and liver collagen deposits, while increased its antioxidant, anti-inflammatory and anti-apoptotic effects. In conclusion, carvedilol protects against H-IRI in HFrHFD-fed mice. GRK2 and GRK5 may not play a potential role in mediating this effect.
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Eslam Ahmed Abdelhamid ebrahiem, "GSK-3 heterozygous knockout is cardioprotective in a knockin mouse model of familial dilated cardiomyopathy", Am J Physiol Heart Circ Physiol, 2016
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Eslam Ahmed Abdelhamid ebrahiem, "β-arrestin-mediated signaling improves the efficacy of therapeutics.", J-STAGE, 2012
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Eslam Ahmed Abdelhamid ebrahiem, "Ameliorative effects of clonidine on ethanol induced kidney injury in rats: Potential role for imidazoline-1 receptor.", zagizag, 2018
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Department Related Publications
Hanan Hamdy Mahmoud Ibrahiem, "Study on the Molecular Mechanisms Involved Renal tissue injury", لايوجد, 1900
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Rasha Hassan Abdelghani Hassan , "Effect of lansoprazole on gastric secretion, prostaglandin £2 and plasma", لايوجد, 1900
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Nabila Noureldeen Mostafa Elmaraghy, "Pharmacological Studies on the possible Interactions between Some Analgesics", لايوجد, 1900
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Hany Mohamed Abdelmalek Mahmoud ElBassossy, "Heme oxygenase-1 induction protects against hypertension associated with diabetes: effect on exaggerated vascular contractility", Naunyn-Schmiedeberg's Archives of Pharmacology, 2013
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