Role of Gallic Acid in Counteracting Depleted Uranium–Induced Renal Toxicity in Rats: Participation of Redox Stabilizers, Nrf2, NF‐Kb, and Caspase‐3

Abstract

Uranyl acetate (UA), a form of depleted uranium (DU) extensively applied for military and civilian purposes, poses a health threat to exposed populations. Gallic acid (GA), a phytochemical present in various edible sources, has the potential to restore redox balance and exhibit anti‐inflammatory and antiapoptotic effects. Thus, we highlighted the potential protective role of GA in mitigating UA‐induced renal cytofunctional impairments in rats. To achieve this objective, the rats were randomly divided into three groups. The first group was left untreated and served as the control. The second group (UA group) was administered a single intraperitoneal injection of UA at a dose of 5 mg/kg body weight. The third group (GA + UA) GA was orally administrated GA via a gastric tube at a dose of 20 mg/kg body weight for 14 days prior to the UA injection. In both the second and third groups, UA was administered on the 15th day, and the rats were euthanized on the 17th day of the experiment. At the end of the experiment, plasma renal damage biomarkers, renal redox parameters, and histopathological examination were estimated, along with immunohistochemical analysis of caspase‐3, nuclear factor kappa B (NF‐kB), and nuclear factor erythroid 2‐related factor 2 (Nrf2). Our findings indicated that GA supplementation in UA‐intoxicated rats reduced plasma urea and creatinine levels while increased total antioxidant capacity. It also restored normal kidney levels of superoxide dismutase, catalase, reduced glutathione, and nitric oxide. Additionally, it restored kidney glycogen reserves and decreased collagen fiber deposition. In the GA + UA group, immunoreaction levels of caspase‐3 and NF‐kB decreased, while those of Nrf2 increased. In summary, GA has the potential to mitigate DU‐associated nephrotoxicity by enhancing the antioxidant defense mechanism, as well as modulating protein expression related to cell death pathways and proinflammatory transcription factors.