Nicotinamide and methionine reduce the liver toxic effect of methotrexate.
Methotrexate is widely used as a therapeutic agent in different diseases. This therapy is connected with various side effects, including liver toxicity. We have developed a mouse model to demonstrate the toxic effects of methotrexate: mice were given 50 mg/kg acetaminophen, which itself has no effect on the liver. If, additionally, methotrexate is applied, there is an increase 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 methotrexate application is markedly reduced. On the basis of these results, it can be concluded that methotrexate therapy should be combined with either nicotinamide or methionine, respectively.
Kröger
H
H
Deutsches Rheumaforschungszentrum Berlin, Germany.
Hauschild
A
A
Ohde
M
M
Bache
K
K
Voigt
W P
WP
Thefeldt
W
W
Krüger
D
D
D000082:Acetaminophen / Q000627:therapeutic use; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004359:Drug Therapy, Combination; D008107:Liver Diseases / Q000188:drug therapy; D008297:Male; D008715:Methionine / Q000627:therapeutic use*; D008727:Methotrexate / Q000009:adverse effects*; D051379:Mice; D008811:Mice, Inbred DBA; D009536:Niacinamide / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D018501:Antirheumatic Agents; D009536:Niacinamide; D000082:Acetaminophen; D008715:Methionine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008727:Methotrexate