Investigating the potential beneficial effects of gallic acid in the treatment of diatriazoate-induced nephropathy in rats: NRF2/Keap-1/HO-1 pathway

The rising use of radiological imaging has significantly increased the administration of contrast media and the incidence of iatrogenic renal dysfunction. Contrast media nephropathy (CMN) is defined by a serum creatinine rise exceeding 25% or 0,5 mg/dL within 24-72 hours post-exposure. CMN's pathophysiology is complex, involving increased oxidative stress, renal vasoconstriction, and suppression of antioxidant defenses. The NRF2/Keap-1/HO-1 signaling pathway regulates oxidative stress. NRF2 activation mitigates oxidative stress effects by enhancing cellular detoxification enzymes, while HO-1 has tissue-protective functions by releasing antioxidant components through heme degradation. Gallic acid, a polyphenolic compound, exhibits strong antioxidant and anti-inflammatory effects. Its capability to inhibit cell death through anti-apoptotic and anti-inflammatory properties indicates a potential protective role. This study investigates the protective and therapeutic effects of gallic acid against nephrotoxicity induced by diatrizoate in rats. The experiment involved administering diatrizoate to induce nephropathy in rats over one day, followed by euthanasia and histopathological evaluation via hematoxylin and eosin staining. Immunohistochemistry and biochemical methods assessed inflammation and apoptosis. The expressions of the NRF2/Keap-1/HO-1 gene were evaluated alongside urea and creatinine levels. Results indicated a significant increase in urea and creatinine in the URO group compared to controls, with reductions in the URO+GA group. Additionally, total oxidative status (TOS) increased markedly in the URO group, while GA treatment resulted in a significant decrease. Total antioxidant status (TAS) decreased in the URO group but increased significantly with GA treatment. Moreover, Caspase-3 and TNF-α levels rose significantly in the URO group, whereas GA administration reduced these expressions. In conclusion, the findings suggest that gallic acid provides protective effects against the mechanisms involved in CMN, warranting further exploration as a potential therapeutic agent Keywords: Gallic acid, HO-1, contrast media nephropathy, Keap-1, Nrf2, oxidative stres