Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits

Abstract

Objectives:To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity.Materials and Methods:Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed.Results:Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments.Conclusion:Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection.

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

“…These findings go in hand with Zubairi et al, [34] who detected histopathological changes of hepatotoxicity in all APAP-treated rabbits, but completely disappeared in 50%, while was mild in 50% of CVD-treated rabbits. Also, they found serum liver function tests and MDA in serum and liver homogenate were elevated with depleted GSH after APAP treatment, in CVD-treated rabbits while MDA and ALP levels were significantly decreased.…”

The Protective Effect of Nitroglycerin, N-Acetyl Cysteine and Metoprolol in CCL4 Induced Animal Model of Acute Liver Injury

“…The antioxidant effect of metoprolol in vitro has been studied and described previously [1]. The antioxidant properties of metoprolol in vivo are a little bit query as there is only one study showing a little hepatoprotective effect [2]. Many drugs with putative antioxidant effects require high concentration or show antioxidant effects only under in vitro conditions.…”

“…Acute liver injury (ALI), is a clinical state that results from severe and extensive damage of liver tissue with reduced cell mass and blood flow. It is associated with an increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALT), and total serum bilirubin (TSB) [1], [2], [3].…”

Prazosin Protects the Liver Against Renal Ischemia/Reperfusion Injury in Rats

“…The usefulness of alpha1-adrenoceptor (α1-AR) antagonists against I/R injury has been reported [16,17]. Evidence indicates that blocking of alpha1-adrenoceptor (α1-AR) can overcome the harmful effects of I/R by increasing the levels of anti-inflammatory factors and decreasing pro-inflammatory cytokines [18].…”