Curcumin as a nephroprotective agent against isoniazid and rifampicin-induced kidney toxicity: A histopathological and molecular docking study

Abstract

Aim: Isoniazid (INH) and rifampicin (RIF) are the main drugs used in the treatment of tuberculosis; however, their combined use can lead to kidney damage through oxidative stress and inflammation. Curcumin, a natural polyphenol derived from Curcuma longa, holds promise in reducing drug-induced nephrotoxicity due to its antioxidant and anti-inflammatory properties. This study investigated whether curcumin protects against kidney damage induced by INH and RIF.

Methods: INH and RIF (100 mg/kg each) were administered to Wistar rats in combination (INH+RIF), either alone or together with curcumin (100 mg/kg). The animals were sacrificed after 24 hours, 7 days, and 14 days, and their kidneys were collected. Histological evaluation was performed with H&E, PAS, and Masson's trichrome stains, and quantitative morphometric analyses were performed for Bowman’s capsule diameter, glomerular diameter, and Bowman’s space area. In parallel with the study, the interaction of curcumin with inducible nitric oxide synthase (iNOS) was investigated by molecular docking and compared with that of resveratrol, quercetin, and N-acetylcysteine amid.

Results: Significant glomerular shrinkage, tubular damage, and inflammatory cell infiltration were observed in the INH+RIF group. Curcumin co-treatment preserved renal architecture and attenuated these changes. Docking showed that curcumin formed stable H-bonds and π–π interactions with key residues of iNOS (Tyr489, Cys200), and its binding energy (−7.08 kcal/mol) was more favorable than that of resveratrol (−5.54), quercetin (−4.89), and N-acetylcysteine ​​amide (−3.16 kcal/mol).

Conclusions: Curcumin attenuated INH/RIF-induced kidney injury; this effect is consistent with docking findings suggesting that iNOS-related oxidative pathways may be limited. The findings support curcumin as a potential co-therapy candidate to improve renal safety during tuberculosis treatment.