ABSTRACT Methotrexate (MTX), a common chemotherapeutic and immunosuppressive drug, is limited by dose‐dependent nephrotoxicity mediated by oxidative stress, mitochondrial dysfunction, and apoptosis. L‐carnitine (LCR), a mitochondrial cofactor with antioxidant and anti‐apoptotic properties, may counteract these mechanisms. This study aims to determine whether LCR mitigates MTX‐induced nephrotoxicity by rebalancing the BAX/BCL2 apoptotic axis and preserving renal compartment integrity (endothelial CD31, tubular cytokeratin, podocyte WT1). Twenty‐four female Wistar rats were randomized into Control, MTX (20 mg/kg, i.p., Day 5), LCR (200 mg/kg/day, i.p., 10 days), and MTX + LCR groups ( n = 6 each). Renal injury was assessed by serum creatinine, urea, BUN, histopathology, immunohistochemistry (CD31, cytokeratin, WT1), and RT‐qPCR for BAX/BCL2. MTX impaired renal function, caused vascular hyperemia, hemorrhage, and tubular necrosis, increased CD31, cytokeratin, and BAX and decreased WT1 and BCL2. LCR co‐treatment improved biochemical indices, reduced lesions, decreased CD31 and cytokeratin, partially restored WT1 and re‐balanced apoptosis (BAX↓, BCL2↑). LCR disrupts oxidative stress, the mitochondrial apoptosis cascade, and preserves endothelial, tubular, and podocyte integrity in MTX nephrotoxicity.
Türkoğlu et al. (Sun,) studied this question.