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Nicotinamide and methionine reduce the liver toxic effect of methotrexate
H Kröger1, A Hauschild, M Ohde
1Deutsches Rheumaforschungszentrum Berlin, Germany.
Abstract:
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.
Insights
Methotrexate treatment can cause liver damage, but combining it with nicotinamide or methionine significantly reduces these toxic effects and mortality in mice.
Area of Science:
- Pharmacology
- Toxicology
- Hepatology
Background:
- Methotrexate is a crucial therapeutic agent for various diseases.
- Methotrexate therapy is associated with significant side effects, notably liver toxicity.
- Acetaminophen alone does not impact liver function.
Purpose of the Study:
- To establish a mouse model for evaluating methotrexate-induced liver toxicity.
- To investigate the protective effects of nicotinamide and methionine against methotrexate hepatotoxicity.
Main Methods:
- A mouse model was utilized to assess drug toxicity.
- Mice were administered acetaminophen (50 mg/kg) followed by methotrexate.
- The impact of co-administering nicotinamide or methionine with methotrexate was evaluated.
Main Results:
- Methotrexate administration increased mortality and elevated liver enzymes (GOT, GPT).
- Co-administration of nicotinamide or methionine with methotrexate markedly reduced mortality.
- Nicotinamide and methionine significantly decreased elevated GOT and GPT levels caused by methotrexate.
Conclusions:
- Methotrexate therapy poses a risk of liver toxicity.
- Nicotinamide and methionine demonstrate protective effects against methotrexate-induced hepatotoxicity.
- Combining methotrexate therapy with nicotinamide or methionine is recommended to mitigate liver damage.