L-Methionine attenuates methotrexate-induced cardiotoxicity by modulating oxidative stress, inflammation, and dyslipidemia in rats.

Methotrexate (MTX) is a potent chemotherapeutic agent with a wide range of anticancer effects; however, its clinical efficacy is restricted due to its cardiomyopathy. This research examined the protective potential of L-Methionine (L-Met) against MTX cardiotoxicity in rats. Thirty rats were assigned into five groups: control, L-Met 400 (400 mg/kg), MTX (20 mg/kg), MTX + L-Met 300 (20 mg/kg MTX plus 300 mg/kg L-Met), and MTX + L-Met 400 (20 mg/kg MTX plus 400 mg/kg L-Met). L-Met was administered orally for 15 days with a single MTX injection on the 5th day. Serum and cardiac samples were gathered for assessments of cardiac injury markers, lipid profile, atherogenic index markers, redox status markers, and pro-inflammatory cytokines. MTX-induced cardiac damage was demonstrated by elevation in the troponin-I, creatine kinase myocardial band, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase in the serum. Levels of triglycerides, total cholesterol, high- and low-density lipoproteins, atherogenic index, and cardiac risk ratio increased. Notable increase in malondialdehyde, nitric oxide, and protein carbonyl, alongside suppression in reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase, were reported in the cardiac tissue. Furthermore, the inflammatory effect of MTX was demonstrated by elevated C-reactive protein, tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels. In a dose-dependent pattern, the two doses of L-Met significantly attenuated the cardiotoxic effect of MTX, with the higher dose being more effective. In conclusion, L-Met protected against MTX cardiotoxicity in a rat model via attenuating oxidative stress and inflammation, representing preliminary preclinical evidence that warrants further investigation.