Chronic Toxicity of Methotrexate in Rats: Partial to Complete Protection of the Liver by Choline: Brief Communication23

Abstract

Methotrexate (MTX) inhibits the enzyme dihydrofolate reductase, which in turn limits the body's ability to perform transmethylation reactions. This study examined the hypothesis that the consequent deficiency of an important methylated compound, choline, may have contributed to the MTX-induced fatty change in the liver of W rats. Groups of rats were given MTX alone or MTX plus choline in varying dose combinations. All groups but one receiving the combined treatment showed a significantly lower triglyceride concentration in their livers and much less visible hepatocytic fat on histologic examination than did those given MTX alone. The protective effect of choline on the liver was dose related, the unaffected group having received a very small amount. Growth rate, survival, and hematopoietic depression due to MTX were unaltered by choline administration.