Protective Effects of N-Acetylcysteine Plus Coenzyme Q10 Combination Against Atorvastatin-Induced Toxicity: Evidence from In Vivo and In Vitro Experimental Models

Atorvastatin, a widely prescribed HMG-CoA reductase inhibitor, causes statin-associated muscle symptoms and, less commonly, hepatic and renal toxicity, effects attributed to mitochondrial dysfunction and oxidative stress; strategies to prevent this multisystem injury are needed. This study evaluated whether N-acetylcysteine (NAC) and coenzyme Q10 (CoQ10), alone and in combination, protect against atorvastatin-induced toxicity in male BALB/c mice and C2C12 myoblasts. Mice (n = 30) received, by oral gavage once daily for 14 days, vehicle, atorvastatin (100 mg/kg/day), atorvastatin plus NAC (200 mg/kg/day), atorvastatin plus CoQ10 (100 mg/kg/day), or the triple combination. Outcomes included survival, body weight, rotarod performance, serum creatine kinase, erythrocyte oxidative-stress markers, semi-quantitative histopathology, TUNEL apoptosis, and VEGF immunohistochemistry in liver, kidney, and skeletal muscle, complemented by in vitro atorvastatin cytotoxicity and antioxidant cytoprotection assays in C2C12 myoblasts (atorvastatin 50–200 µg/mL; CoQ10 12.5–50 µg/mL; NAC 100–400 µg/mL). Atorvastatin produced significant histopathological injury and increased apoptotic and VEGF immunoreactivity in all three tissues (p < 0.0001–0.005), effects markedly attenuated by combined NAC plus CoQ10. Glutathione peroxidase activity was significantly reduced by atorvastatin and restored by combination therapy (p < 0.05); catalase, malondialdehyde, and superoxide dismutase showed non-significant favorable trends. In C2C12 myoblasts, atorvastatin produced concentration-dependent cytotoxicity (IC50 ≈ 65 µg/mL), substantially reversed by NAC plus CoQ10 (≈89% viability restoration, p = 0.0025). These findings indicate that combined NAC and CoQ10 confer structural, apoptotic, and cytoprotective protection against atorvastatin-induced toxicity, supporting further mechanistic and translational investigation of combined antioxidant strategies in this high-dose supratherapeutic model; extrapolation to routine clinical statin intolerance will require confirmation at clinically relevant exposures.