Protective Effect of Wogonin Against Colistin-Induced Nephrotoxicity in Wistar Rats: A Controlled Experimental Study

Colistin remains a critical antibiotic for treating multidrug-resistant Gram-negative infections, yet its clinical use is severely limited by its high nephrotoxicity profile. There is an urgent need for nephroprotective agents that can mitigate colistin-induced nephrotoxicity (CIN) without compromising antimicrobial efficacy. Wogonin, a flavonoid compound with known antioxidant and anti-inflammatory properties, has shown promise in various models of renal injury, though its potential role in CIN has not been previously evaluated. This study aimed to assess the nephroprotective efficacy of wogonin in a well-characterized Wistar rat model of CIN, using a combination of biochemical, molecular, and histopathological parameters. Thirty adult female Wistar rats were randomly assigned into three groups: control, colistin + tap water, and colistin + wogonin (50 mg/kg/day, oral gavage for 10 days). CIN was induced using a single intraperitoneal dose of colistin (20 mg/kg). Plasma levels of blood urea nitrogen (BUN), creatinine, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured, along with renal tissue levels of SIRT-1 and Nrf2. Histopathological evaluation was performed using a semi-quantitative scoring system. Colistin administration resulted in significant renal dysfunction and tubular injury, as evidenced by elevated biochemical markers and histological damage. Wogonin treatment significantly attenuated elevations in BUN, creatinine, KIM-1, NGAL, MDA, IL-6, and TNF-α, while restoring sirtuin-1 (SIRT-1) and nuclear factor erythroid 2–related factor 2 (Nrf2) levels. Histopathological analysis revealed reduced tubular necrosis, luminal debris, and dilatation in the wogonin group. Wogonin demonstrated significant nephroprotective effects in a rat model of CIN by reducing oxidative stress, suppressing pro-inflammatory cytokine expression, and mitigating tubular epithelial injury.