Protective Effects of 2-Chloro-3-Hydrazinylquinoxaline against Doxorubicin-induced Nephrotoxicity via Modulation of Oxidative Stress and Inflammation in Rats

Abstract

Background: Doxorubicin (DOX) is a widely used anthracycline antibiotic effective against multiple human malignancies, but its clinical utility is limited by well-established nephrotoxicity that frequently manifests as acute kidney injury (AKI). In contrast, the potential nephroprotective effects of 2-chloro-3-hydrazinylquinoxaline (CHQ), a quinoxaline derivative with reported antioxidant and anti-inflammatory properties, remain untested. The present study therefore evaluates whether CHQ can mitigate DOX-induced AKI. Methods: Thirty acclimatized male Wistar rats were randomized distributed into 5 groups: control group; DOX group which received single intraperitoneal (i.p.) injection of DOX (15 mg/kg single) on day 6, DOX + CHQ-30 treated with CHQ (30 mg/kg/day orally) for 7 days and DOX treatment on day 6; DOX + CHQ-60 group receiving the same regime but with CHQ at 60 mg/kg/day orally and CHQ-60 only received CHQ only at 60 mg/kg/day for 7 days. Key parameters assessed included kidney function biomarkers, oxidative stress markers, anti-and pro-inflammatory mediators (IL-1β, IL-6, TNF-α, NF-κB, IFN-γ and COX-2) and additional markers (iNOS, PGE2 and GAPDH). Result: The CHQ treatment significantly ameliorated DOX-induced alterations in biochemical parameters and oxidative stress markers, normalized anti-and pro-inflammatory mediator levels and reduced apoptosis-related markers. Histopathological analysis also supports the renoprotective effect. These findings demonstrate that CHQs possess significant antioxidant and anti-inflammatory properties, suggesting their therapeutic potential to attenuate DOX-induced nephrotoxicity.