Background: Mercuric chloride (HgCl₂) causes renal injury partly through oxidative stress and inflammation. This study investigated the protective effects of gallic acid (GA) against HgCl₂-induced nephrotoxicity in rats.
Methods: Thirty-five Wistar rats were randomly assigned to five groups (n = 7): control, HgCl₂ (0.4 mg/kg/day), HgCl₂ plus GA (50 or 200 mg/kg/day), and GA alone (200 mg/kg/day). Treatments were administered orally for 28 days, with GA given 1 h before HgCl₂. Renal function was assessed using serum blood urea nitrogen (BUN), creatinine (Cr), kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Renal tissue was analyzed for malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and renal histopathology.
Results: HgCl₂ significantly increased serum BUN, Cr, KIM-1 and NGAL, renal MDA, TNF-α, IL-1β, while reducing GSH content and SOD, CAT, and GPx activities. GA at both doses improved several of these changes. The 200 mg/kg GA dose reduced both KIM-1 and NGAL and produced a greater reduction in histopathological injury than the 50 mg/kg dose. However, several inflammatory and injury markers remained above control levels, indicating incomplete protection.
Conclusion: GA attenuated multiple biochemical and histological changes associated with HgCl₂-induced renal toxicity in rats. Its effects were associated with improved antioxidant status and lower inflammatory and kidney injury markers. Further studies are needed to establish the underlying mechanisms and clinical relevance.
Mechanistic and Translational Relevance: Gallic acid may attenuate HgCl₂-induced renal injury by enhancing antioxidant defenses and modulating inflammation, alongside reductions in renal function markers, MDA, TNF-α, IL-1β, KIM-1, and NGAL. The stronger effects observed at the higher dose warrant investigation of dose dependence, although underlying mechanisms remain unclear. Further studies should assess whether these protective effects translate into clinical benefits, as efficacy and safety in humans remain unestablished.