Therapeutic efficacy of Annona muricata in counteracting nephrolithiasis-induced electrolyte imbalance and antioxidant disruption in ethylene glycol-treated rats

Nephrolithiasis (kidney stone) is a global health concern with multifactorial origins, including genetic, environmental, dietary, and metabolic factors. This study investigates the therapeutic potential of Annona muricata (AM) leaf extract in mitigating nephrolithiasis-induced electrolyte imbalance, antioxidant depletion, and histopathological alterations in an ethylene glycol (EG)-challenged rat model by modulating Na⁺/K⁺-ATPase and Ca²⁺/Mg²⁺-ATPase activities. Twenty-five male rats were randomly assigned to five experimental groups: 0.75% v/v ethylene glycol in drinking water for 28 days in the other groups, except the control (NC) group. The control (NC) and ethylene glycol-induced (EG) groups received distilled water, while other treatment groups were administered Zyloric (2 mg/kg/day), low-dose AM (200 mg/kg/day; EG + AML), and high-dose AM (800 mg/kg/day; EG + AMH) for 21 days. EG-induced disturbances in magnesium, sodium, potassium, chloride and calcium concentrations were effectively counteracted by both AM doses (200 mg/kg and 800 mg/kg/day) and Zyloric, with restorative effects on calcium levels of 8.02%, 18.18%, and 8.53%, and on magnesium levels of 12.77%, 25.24%, and 22.44%, respectively. Our findings suggest that AM exerts nephro-restorative effects by modulating electrolyte balance, ameliorating nephrolithiasis-induced histopathological changes, and enhancing antioxidant defences, as well as Na⁺/K⁺-ATPase and Ca²⁺/Mg²⁺-ATPase activities. These results showed the potential of AM as a therapeutic candidate for kidney stone management and related renal dysfunctions. Conclusively, AM exhibited therapeutic potential against ethylene glycol (Nephrolithiasis)-induced electrolyte imbalance, antioxidant depletion, and histopathological changes.