THE POTENTIAL BENEFICIAL EFFECT OF BEMPEDOIC ACID ON METHOTREXATE-INDUCED HEPATOTOXICITY IN RATS VIA THE ACTIVATION OF AMPK PATHWAY

Abstract

More than a thousand medications have been related to hepatotoxicity, A variety of clinical symptoms may be associated with it, or it may appear as a silent subclinical illness. Folic acid antagonist methotrexate (MTX) is frequently used as a cytotoxic medication to treat a range of illnesses, including leukaemia and inflammatory diseases like psoriasis and rheumatoid arthritis. However, because of its deadly adverse effects, particularly hepatotoxicity, its use in clinical practice has been restricted.   This study aimed to evaluate the impact of bempedoic acid on the liver damage caused by MTX in rats. The rats were divided into four groups: bempedoic acid (BEM) (30 mg/kg/day p.o.), MTX (14 mg/kg/week i.p.), MTX with bempedoic acid, and control. The animals were killed on the fifteenth day so that histopathological and biochemical tests could be conducted. The liver damage was evaluated by looking at histopathologic changes. Tissue malondialdehyde (MDA), glutathione peroxidase (GSH), catalase (CAT), superoxide dismutase, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also assessed. According to our findings, MTX treatment considerably alleviated the histopathologic changes and increased MDA, AST, and ALT levels brought on by MTX administration. Bempedoic acid therapy also markedly increased the activities of GSH, CAT, SOD, and AMPK. Nonetheless, a number of advantages were noted with the bempedoic acid dosage. According to our findings, bempedoic acid may protect liver tissue from MTX-induced hepatotoxicity by preventing oxidative stress.