Nicotinamide and methionine reduce the liver toxic effect of methotrexate

Methotrexate is widely used as a therapeutic agent in different diseases. T his therapy is connected with various side effects, including liver toxicit y. We have developed a mouse model to demonstrate the toxic effects of meth otrexate: mice were given 50 mg/kg acetaminophen, which itself has no effec t on the liver. If, additionally, methotrexate is applied, there is an incr ease in the death rate, as well as in glutamate-oxaloacetate transaminase ( GOT) and glutamate-pyruvate transaminase (GPT) activities. If methotrexate is administered in conjunction with either nicotinamide or methionine, the rise in the death rate and in GOT and GPT activities associated with methot rexate application is markedly reduced. On the basis of these results, it c an be concluded that methotrexate therapy should be combined with either ni cotinamide or methionine, respectively. (C) 1999 Elsevier Science Inc. All rights reserved.