Abstract:


Methotrexate (MTX), the antiproliferative, anti-inflammatory, and immunosuppressive drug is one of the most effective drugs used for the treatment of a large number of solid tumours, hematologic malignancies, and autoimmune disorders. However, its significant hepatotoxicity limits its applicability, so this study was suggested to investigate the side effects of a high dose of MTX on the liver in experimental rats. Ten rats were divided randomly into two groups, including the control group and MTX-injected group. MTX group received a single dose of 40 mg/kg MTX intraperitoneally to induce liver injury. Physiological saline was injected into the control rats in the same manner. The period of the experiment was 14 days. At the end of the experiment, the rats were sacrificed. Sera and liver specimens were then collected for the evaluation of hepatic function by measurement of aspartate transaminase  (AST) and alanine transaminase (ALT) serum levels and histological examination of liver tissues. The results showed that MTX administration induced a highly significant increase in serum AST and ALT levels. Additionally, the histopathological examination of livers indicated the presence of clear vacuoles in the hepatocytes, hydropic degeneration, and multi-focal necrosis.  Additionally, there was mononuclear cell infiltration and Kupffer cellular hyperplasia. Congestion, desquamation of lining endothelial cells in some blood vessels, and haemorrhages were also detected. Therefore, we concluded that administration of high doses of MTX induced severe hepatotoxicity in experimental rats manifested by a significant increase of liver enzymes in serum and severe alteration in the liver histological structure.