L-Carnitine Attenuates Methotrexate-Induced Nephrotoxicity by Modulating BAX/BCL2 Apoptotic Signaling and Preserving Podocyte, Endothelial, and Tubular Integrity
Journal of Applied Toxicology, cilt.46, sa.9, ss.3102-3112, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 46 Sayı: 9
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/jat.70096
- Dergi Adı: Journal of Applied Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, EMBASE, Environment Index, MEDLINE
- Sayfa Sayıları: ss.3102-3112
- Anahtar Kelimeler: BAX/BCL2, endothelial dysfunction, L-carnitine, methotrexate, mitochondrial apoptosis, nephroprotection, nephrotoxicity, oxidative stress
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
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.