Effect of carvedilol versus propranolol on acute and chronic liver toxicity in rats

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) Vol. 44; no. 1; pp. 101 - 111
• Main Author: Abdel-Kawy, Hala Salah
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.01.2021
• Subjects: Acetaminophen; Adrenergic beta-Antagonists - pharmacology; Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Biomarkers - blood; Carbon Tetrachloride; Carvedilol; Carvedilol - pharmacology; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Chemical and Drug Induced Liver Injury, Chronic - etiology; Chemical and Drug Induced Liver Injury, Chronic - metabolism; Chemical and Drug Induced Liver Injury, Chronic - pathology; Chemical and Drug Induced Liver Injury, Chronic - prevention & control; Glutathione - metabolism; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Cirrhosis, Experimental - chemically induced; Liver Cirrhosis, Experimental - metabolism; Liver Cirrhosis, Experimental - pathology; Liver Cirrhosis, Experimental - prevention & control; Male; Malondialdehyde - metabolism; Oxidative Stress - drug effects; paracetamol; propranolol; Propranolol - pharmacology; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha - blood; β-blockers; β-blockers; paracetamol; liver; Carvedilol; propranolol
• ISSN: 0148-0545; 1525-6014
• DOI: 10.1080/01480545.2019.1576718

Non-selective β-blockers have largely been used for prophylaxis of bleeding from gastroesophageal varices, but their hepatic effects and their influence on the development of varices has yet to be clarified. This study examined whether carvedilol would reduce acute and chronic liver injury in rats in comparison to propranolol. Experiment (1) Investigated the effects of carvedilol (1.2 mg/kg) and propranolol (4.0 mg/kg) administered daily for 7 days by gavage on paracetamol (1500 mg/kg i.p.) -induced acute liver injury in rats. Experiment (2) Investigated the effects of carvedilol (1.2 mg/kg) and propranolol (4.0 mg/kg) by gavage daily for 8 weeks on CCl 4 -induced chronic liver injury in rats. Biochemical markers and histopathology of the livers were studied. Liver perfusion studies were carried out on CCl 4 treated rats. Experiment (1) Carvedilol significantly improved the functional state of the liver in paracetamol-induced acute toxic hepatitis to a greater extent than propranolol. This was evidenced by a greater reduction in elevated serum levels of ALT and AST, hepatic MDA and TNF-α, attenuation of the paracetamol-induced decrease in GSH, together with improvement in the histological architecture of the liver. Experiment (2) Carvedilol was superior to propranolol against CCl 4 -induced hepatic injury and fibrogenesis. It suppressed hepatic inflammation, attenuated hepatic oxidative stress, and inhibited HSC activation. Carvedilol also decreased portal perfusion pressure. These results suggest that carvedilol might be a therapeutic anti-fibrogenic candidate against hepatic fibrosis, protecting the liver from acute and chronic toxic injury, in addition to lowering portal pressure.