Abstract
Methotrexate (MTX) and azathioprine (AZA) are chemotherapeutic, antimetabolic, and immunosuppressive agents with substantial risks such as oxidative lesions to the liver. This study examined the effect of grape seed extract (GSE; gervital) in attenuating hepatotoxicity caused by MTX or AZA treatment. Rats were divided into six groups (six rats per group): Group I, normal control group; Group II, GSE (150 mg/kg/day); Group III, MTX (8 mg/kg/week); Group IV, AZA (15 mg/kg/day); Group V, GSE (150 mg/kg/day) + MTX (8 mg/kg/week); and Group VI, GSE (150 mg/kg/day) + AZA (15 mg/kg/day). After 35-day experimental period, all rats were sacrificed and blood was collected for biochemical study and hemoglobin (Hb) assessment. The liver was weighed and triaged for histological, ultrastructural, and biochemical studies. MTX and AZA treatment decreased Hb levels, increased relative liver weight, increased the activity of glutamate pyruvate transaminase (ALT) and glutamate oxaloacetate transaminase (AST) aminotransferase (ALT) and aspartate aminotransferase (AST) values, and displayed histopathological and ultrastructural alterations. These changes included the disorganization of hepatocytes, pyknosis, karyolysis of some nuclei, and mononuclear leukocytic infiltration. The liver with significant oxidative stress (OS) showed decreased reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and increased malondialdehyde (MDA) levels. In contrast, GSE administration ameliorated ALT, AST, and all histopathological and ultrastructural changes. GSE treatment also reduced MDA levels but increased the antioxidant parameters. In conclusion, it was concluded that GSE supplementation could be considered as a promising antioxidant in reducing OS, histopathological and ultrastructural alterations induced by MTX and AZA.
Graphical abstract