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In non-alcoholic fatty liver disease, several pathophysiological arguments suggest (in the absence of proof from clinical trials) that long-term methotrexate therapy worsens liver damage and the progression of liver disease

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This mechanism is critical because neurons have a limited ability to synthesize endogenous GS ( Oxidative stress in the CNS acts as a persistent inflammatory trigger by activating brain-resident immune cells, particularly microglia and astrocytes