Methotrexate hepatotoxicity.

An inhibitor of folate metabolism, amethopterin (methotrexate) has been successfully used in the treatment of psoriasis and neoplastic disease. This drug produces several dangerous side effects of both an acute and chronic nature which have widely curtailed its use. A serious chronic side effect of the drug is its hepatotoxicity, which may culminate in hepatic cirrhosis and death. To date the underlying mechanism of methotrexate in producing liver damage is unknown. Results of three studies conducted in this laboratory on the nutritional effects of methotrexate offer some evidence that the hepatotoxicity may possibly be incurred through the effect of the drug on methionine biosynthesis and methylation processes. This thesis is discussed in the light of methylating agents vital to the synthesis of methionine.