Dose-dependent therapeutic effects of gum acacia on kidney and metabolic dysfunction in adenine-induced chronic kidney disease in rats: involvement of antioxidant pathways

Abstract

Chronic kidney disease (CKD) poses significant health challenges worldwide, with limited effective natural therapies targeting its progression through antioxidant mechanisms. Although gum acacia (GA) has shown general metabolic benefits, its dose-dependent therapeutic efficacy in CKD and its effects on key antioxidant pathways remain unclear. This study aimed to evaluate the therapeutic potential of gum acacia (GA) in an adenine (AD)-induced CKD rat model. Rats were randomly assigned to five groups (n = 7 per group): Group I (control), Group II (GA at 600 mg/kg for 14 days), Group III (AD at 600 mg/kg for 10 days), and Groups IV and V (AD for 10 days followed by GA at 300 mg/kg or 600 mg/kg for 14 days). All treatments were administered daily by oral gavage. AD treatment led to significant reductions in body weight, increased relative kidney weight, and disrupted kidney and liver function markers, including elevated urea, creatinine, ALT, GGT, and glucose levels. AD also increased oxidative stress, altered blood parameters, and caused downregulation of APRT mRNA expression and upregulation of FGF-23 expression. GA treatment at both doses (300 and 600 mg/kg) mitigated these abnormalities, significantly improving kidney and liver function, enhancing antioxidant status, and ameliorating hematological and metabolic disturbances. The most pronounced effects were observed with the 600 mg/kg dose. Building on prior indications of GA’s benefits, our findings offer new and comprehensive evidence of its dose-dependent therapeutic effects in adenine-induced CKD, particularly through the modulation of oxidative stress pathways and regulation of APRT and FGF-23 expression. These insights lay the groundwork for future clinical translation.