Therapeutic Effects of Gallic Acid and Alpha-Tocopherol on Adenine-Induced Chronic Kidney Disease in Male Wistar Rats.

Abstract

Chronic kidney disease (CKD) is a major health issue associated with oxidative stress and inflammation that leads to progressive renal damage. Natural antioxidants, gallic acid (GA) and alpha-tocopherol (AT), have gained attention for their strong free radical-scavenging, inflammation-reducing, and tissue-repairing properties, and their individual or combined administration may offer therapeutic potential in CKD management. This experiment was designed to explore the potential ameliorative effects of GA and AT against CKD induced by adenine in male rats. Adult rats weighing 180-220 g (n = 48) were distributed among eight experimental groups. Except for Group I (control), all groups received a standard rat diet supplemented with 0.75% (w/w) adenine for 4 weeks to induce CKD. During the same period, the experimental groups received oral treatments of GA and AT at doses of 100 and 400 mg/kg body weight, respectively, as well as their combinations (GA-AT) at the same doses. The treatments were administered simultaneously for 4 weeks to evaluate their effects on adenine-induced CKD. The results indicated that both GA and the combination of GA-AT were significantly more effective than AT alone in improving renal function markers such as uric acid, creatinine, albumin, and urea. Additionally, these treatments led to better outcomes for serum concentrations of these markers and oxidative stress biomarkers. Histopathological analysis confirmed the beneficial effects on kidney tissue compared to the diseased group. Moreover, both GA and the GA-AT combination treatments showed superior results in the relative expression of mRNA markers related to kidney function, including Igfbp7, Vcam1, and Timp2. Molecular docking studies demonstrated notable binding affinities and interactions between key kidney markers and selected GA and AT compounds. These findings suggest that GA, particularly in combination with AT, effectively restores kidney function in adenine-induced CKD, supporting further research to optimize their clinical applications in CKD management.