Comparative study of the protective effects of adenosine triphosphate and resveratrol against amiodarone-induced potential liver damage and dysfunction in rats.

Abstract

Background: Amiodarone is the most commonly used class III antiarrhytmic drug with antiarrhytmic and vasodilator properties. Adenosine triphosphate (ATP) serves as a crucial source of intracellular energy, while resveratrol is known for its potent antioxidant activity.

Objectives: This study aimed to biochemically, histopathologically and immunohistochemically evaluate the effects of ATP, resveratrol and their combination on potential liver damage and dysfunction induced by amiodarone in rats.

Material and methods: The rats were divided into 6 groups: healthy control (HG), amiodarone alone (ADG), amiodarone + ATP at 2 mg/kg (AAG-2), amiodarone + ATP at 5 mg/kg (AAG-5), resveratrol + amiodarone (RAG), and resveratrol + amiodarone + ATP at 2 mg/kg (RAA-2). Amiodarone (50 mg/kg, orally), ATP (2 mg/kg and 5 mg/kg, intraperitoneally) and resveratrol (25 mg/kg, orally) were administered once daily for 14 days. Following treatment, liver tissues were excised for biochemical analysis. Oxidative stress was assessed by measuring malondialdehyde (MDA) levels, while antioxidant status was evaluated through total glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. To assess liver function, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in serum samples collected from the animals' tail veins. In addition, liver tissues were subjected to histopathological and immunohistochemical examination to evaluate structural and molecular changes associated with treatment.

Results: Amiodarone administration led to a significant increase in oxidative stress markers and a reduction in antioxidant levels in rat liver tissue. Additionally, serum levels of ALT and AST were elevated, indicating liver dysfunction. Histopathological and immunohistochemical analyses revealed severe (grade 3) oxidative damage in the liver tissue. All biochemical parameters in the 5 mg/kg ATP and resveratrol + 2 mg/kg ATP treatment groups were comparable to those observed in the HG group. Histopathological and immunohistochemical evaluations showed a reduction in liver damage severity to grade 2 in the groups treated with ATP (2 mg/kg) and resveratrol alone, and to grade 1 in the groups receiving ATP (5 mg/kg) or the combination of resveratrol + ATP (2 mg/kg).

Conclusions: The results of the present study suggest that adjusting the ATP dosage or using a combination of ATP and resveratrol may be effective strategies for minimizing amiodarone-induced liver damage.