Nephroprotective Potential of <i>Olea europaea</i> Leaf Extract Against Combined Noise and Toluene‐Induced Oxidative and Histopathological Renal Injuries in Wistar Rats

Abstract

Noise and toluene are environmental stressors that induce oxidative stress and inflammation, contributing to renal dysfunction. This study evaluated the protective effects of Olea europaea leaf extract (OeLE; 40 mg/kg/day) against combined noise- and toluene-induced nephrotoxicity in Wistar rats. Forty-eight male rats were divided into eight groups and exposed for 6 weeks (6 h/day, 5 days/week) to noise, toluene, or their combination, with or without OeLE supplementation. Renal function biomarkers (urea and creatinine), oxidative stress indices (malondialdehyde, catalase [CAT], and superoxide dismutase [SOD]), histopathology, and in silico docking targeting key redox and inflammatory mediators (CAT, SOD, IL-1β, TNF-α, and NF-κB) were assessed. Co-exposure caused significant renal dysfunction, elevated lipid peroxidation, impaired antioxidant defenses, glomerular collapse, tubular necrosis, vascular congestion, and interstitial inflammation, with the combined exposure group showing the most severe lesions. OeLE supplementation markedly mitigated these effects by restoring renal biomarkers, reducing oxidative injury, enhancing enzymatic antioxidant activity, and preserving renal architecture. Molecular docking confirmed strong interactions between OeLE bioactive compounds (oleuropein and luteolin-7-O-glucoside) and antioxidant/inflammatory mediators. OeLE exerts antioxidant and anti-inflammatory effects, protecting the kidneys from combined noise- and toluene-induced damage, highlighting its potential as a natural therapeutic agent.