Rutin attenuates colistin-induced nephrotoxicity through modulation of inflammation, oxidative stress, and miRNA-Associated pathways: An experimental study

Colistin is widely used as a last-resort antibiotic for the treatment of multidrug-resistant Gram-negative infections; however, its clinical utility is limited by a high incidence of acute kidney injury. This study investigated the protective effects of rutin, a naturally occurring flavonoid with potent antioxidant and anti-inflammatory properties, against colistin-induced nephrotoxicity and the underlying molecular mechanisms. Male Sprague Dawley rats were divided into control, rutin, colistin, and colistin plus rutin groups and treated with colistin (15 mg/kg/day, intraperitoneally) and/or rutin (50–100 mg/kg/day, orally) for 7 days. Renal function was assessed by measuring serum creatinine and blood urea nitrogen levels. Oxidative stress parameters, tubular injury biomarkers, inflammatory cytokines, regulators of energy metabolism and autophagy, antioxidant- and iron-related proteins, and selected microRNAs and inflammatory signaling pathways were evaluated in renal tissues. Colistin administration caused significant renal dysfunction, as evidenced by increased serum creatinine and blood urea nitrogen levels (p < 0.001), accompanied by marked oxidative stress, inflammatory responses, and tubular injury (p < 0.01). These alterations were associated with suppression of AMP-activated protein kinase signaling and activation of the mammalian target of rapamycin pathway (p < 0.05). Co-administration of rutin significantly attenuated colistin-induced renal injury by reducing oxidative stress and inflammation and restoring energy-metabolic balance (p < 0.05). In conclusion, rutin confers significant protection against colistin-induced nephrotoxicity through coordinated antioxidant, anti-inflammatory, and metabolic regulatory mechanisms, supporting its potential use as an adjunctive agent during colistin therapy.