Cyanidin-3-O-Glucoside in Anthocyanin-Rich Fraction Combined with Atorvastatin Mitigates Kidney Injury via Attenuating Renal Lipotoxicity and Oxidative Stress and Preserving Mitochondrial Function in Obese Rats

Obesity-related kidney injury is associated with renal lipotoxicity, mitochondrial dysfunction, and oxidative stress. This study investigated the potential renoprotective effects of cyanidin-3-O-glucoside (C3G) in an anthocyanin-rich fraction from black glutinous rice (Oryza sativa L.) bran in combination with atorvastatin (ATO) in obese rats. Rats were fed a high-fat diet (HFD) for 16 weeks, followed by 8 weeks of treatment with C3G (100 or 200 mg/kg BW/day) combined with ATO (5 mg/kg BW/day) or ATO alone (10 mg/kg BW/day). HFD increased renal lipid accumulation and oxidative stress and altered mitochondrial-related proteins and renal structure. Both C3G doses combined with ATO 5 mg/kg BW/day improved selected metabolic and renal outcomes. Based on the overall responses, C3G 100 mg/kg BW/day + ATO 5 mg/kg BW/day was selected for subsequent molecular analyses. This combination was associated with reduced renal lipid accumulation and favorable changes in proteins related to lipid metabolism, mitochondrial homeostasis, and oxidative stress, including PPARα, Sirt-1, PGC-1α, MFN2, Parkin, NOX4, Keap1, and Nrf2. Renal MDA levels were also reduced, accompanied by preservation of renal architecture and attenuation of glomerular, tubular, and fibrotic injury. Across several measured outcomes, the renoprotective effects of C3G 100 mg/kg BW/day + ATO 5 mg/kg BW/day were broadly comparable to those of ATO 10 mg/kg BW/day. These findings support further investigation of C3G combined with ATO as a potential adjunctive strategy for obesity-associated kidney injury.