Evaluation of the possible protective role of folic acid on the liver toxicity induced experimentally by methotrexate in adult male albino rats

ABSTRACT

Methotrexate [MTX] is a chemotherapeutic drug that is widely used in the treatment of malignant tumors and rheumatic disorders. However, the clinical success is limited by the hepatotoxic effect which is a major adverse reaction that can occur during [MTX] treatment. The present study was designed to throw the light on the histological changes in the rat liver following treatment with [MTX] with evaluation of the possible protective effect of folic acid. Thirty two adult male albino rats were utilized in the present work. They were classified into four groups [8 animals each]. Group I Served as control group. Group II The rats received folic acid in a daily oral dose of [250ug/kg b.w] for four weeks. Group III Included rats which received an I.P injection of MTX [20mg/kg b.w] once weekly for four weeks. Group IV The animals were concomitantly treated with MTX and FA as the same previous doses, period and routes of administration for four weeks. Blood samples were collected from retroorbital venous plexus for biochemical measurements of liver enzymes [transaminases] in the serum, then the animals were sacrificed by decapitation. Specimens from the liver were processed for light and electron microscopic studies. The present work showed severe damage of the rat liver following [MTX] treatment as denoted by increased levels of aspartate transaminase [AST] and alanine transaminase [ALT] enzymes in the serum. Examination of the liver sections revealed severe dilatation and congestion of the central and portal veins with marked mononuclear cellular infiltration. Hepatocellular vacuolation with areas of fatty degeneration could be clearly seen. Increased collagen deposition especially around the portal areas was observed in addition to depletion of glycogen content. The activity of succinic dehydrogenase enzyme was apparently decreased while that of acid phosphatase was greatly increased. Severe damage of the cell organdies was obviously seen. On the other hand, rats received folic acid [FA] following treatmeIlt with MTX revealed more or less apparent normal architecture. FA proved to have remarkable protective effect against toxicity of MTX by minimizing the previous degenerative changes, so it is advisable for patients routinely treated with [MTX]