Our study demonstrated that a novel pyridinone drug, mefunidone, effectively ameliorated IRI-induced AKI by suppressing oxidative stress, maintaining mitochondrial structure, inhibiting kidney tubular epithelial cell apoptosis by regulating mitochondrial-related Bax/bcl2/cleaved-caspase3 apoptotic protein expression, and protecting mitochondrial electron transport chain complex III and complex V levels. This evidence concerns the gene BCL2 and acute kidney injury.