Protective Role of 2,3-Dimethylquinoxaline Against Doxorubicin-Induced Renal Inflammation in Rats via Modulation of the iNOS/COX-2/PGE2/TNF-α/NF-κB Signaling Pathway

Background: A member of the quinoxaline family, 2,3-dimethylquinoxaline (DMQ), has been evaluated for associated nephroprotective properties in an in vivo model system to assess renal inflammation induced by the anticancer drug doxorubicin (DOX). Methods: Rats were administered DMQ at doses of 30 or 60 mg/kg body weight once daily for 7 consecutive days. Additionally, a single intraperitoneal (i.p.) dose of DOX (15 mg/kg body weight) was administered on the sixth day. DMQ-mediated nephroprotective effects were assessed by measuring renal function markers, oxidative stress markers, lipid peroxidation, renal stress markers, proinflammatory cytokines, and inflammatory mediator levels, as well as by performing histopathological examination of kidney tissues. Results: DMQ-treated rats exhibited a marked reduction in kidney toxicity markers and restoration of antioxidant enzyme levels, leading to attenuated oxidative stress. DMQ administration also reduced proinflammatory cytokines, renal stress markers, and inflammatory mediators. Furthermore, DMQ may also attenuate DOX-induced renal structural damage and help restore the dilated capsular space and other histopathological alterations in kidney tissues. Conclusion: These findings suggest that DMQ may protect against DOX-induced renal damage by alleviating oxidative stress and inflammation in a rat model, indicating the potential of DMQ as a nephroprotective agent.