Nephroprotective Effects of Ethanol and Fomepizole in a Methotrexate-Pretreated Rat Model of Methanol Intoxication

Methanol intoxication causes metabolic acidosis, organ injury, and death; renal injury predicts adverse outcomes. Ethanol and fomepizole were compared in a methotrexate-pretreated rat model of methanol intoxication. Thirty male Wistar rats were allocated to five groups: Control, methotrexate (MTX), MTX + Methanol, MTX + Methanol + Fomepizole, and MTX + Methanol + Ethanol (n = 6 per group). MTX was administered by oral gavage at 0.3 mg/kg/day on days 1-7. The three methanol-exposed groups received 3 g/kg methanol by oral gavage on day 8. Fomepizole was administered intraperitoneally at 15 mg/kg 4 h after methanol administration, followed by 10 mg/kg at 12, 24, and 36 h. Ethanol was administered once by oral gavage at 0.5 g/kg 4 h after methanol administration. Samples were collected on day 10. No primary outcome was prospectively designated. Renal function, kidney homogenate injury, inflammatory biomarkers, blood-derived redox-related biomarkers, and histopathological findings were assessed. Analysis of variance (ANOVA) revealed significant group differences in kidney-homogenate cystatin C (p = 0.003), interleukin-6 (IL-6; p = 0.013), kidney injury molecule-1 (KIM-1; p = 0.017), serum urea (p = 0.017), and serum creatinine (p < 0.001). Duncan post hoc testing showed lower values for these parameters in both antidote groups than in the MTX + Methanol group. No significant biochemical differences were identified between the two antidote groups. Histopathological scores were lower in the antidote groups. Although fomepizole showed a more favorable descriptive pattern, the findings do not establish its superiority over ethanol. Variance heterogeneity, multiple testing, unequal antidote regimens, the absence of toxicokinetic and acid-base measurements, and short follow-up limit interpretation. Future studies should include direct measurements of methanol and formate, renal cytosolic alcohol dehydrogenase activity, correlations with renal biochemical outcomes, longer follow-up periods, and comparable antidote regimens.