Nephroprotective Activity of Manilkara Zapota Nano-Suspension Formulation on Gentamicin Induced Nephrotoxicity in Rat Model

Background:  Nephrotoxicity is a major cause of acute kidney injury (AKI) due to toxic drug exposure. Gentamicin, a widely used aminoglycoside antibiotic, induces renal damage through oxidative stress, inflammation, and lipid peroxidation. Herbal drugs with antioxidant properties are being explored as safer alternatives to NSAIDs. Manilkara zapota (Sapota) is rich in flavonoids, tannins, and polyphenols, with proven antioxidant and anti-inflammatory effects. Objective: This study aimed to evaluate the nephron-protective effect of the hydroalcoholic extract of Manilkara zapota (HAMZ) and its ethanolic nanosuspension (EENs) formulation against gentamicin-induced nephrotoxicity in Wistar rats by assessing biochemical, antioxidant, and histopathological parameters. Materials and methods: Gentamicin (100 mg/kg, i.p.) was administered for eight days to induce nephrotoxicity. The rats were divided into five groups: normal control, disease control, standard (selenium 2 mg/kg), EENs (200 mg/kg), and HAMZ (400 mg/kg). Serum and urine samples were analyzed for creatinine, BUN, uric acid, calcium, phosphorus, and magnesium levels. Antioxidant markers (SOD, CAT, GSH, and LPO) and kidney histology were evaluated. Results: Gentamicin caused significant elevation of serum creatinine, BUN, uric acid, and LPO levels with a decline in antioxidant enzymes. Treatment with HAMZ and EENs significantly restored renal function and antioxidant status, reducing tubular necrosis and inflammation in the kidneys. The 400 mg/kg HAMZ dose showed results comparable to those of selenium. Conclusions: The Manilkara zapota extract and its nano-suspension exhibited strong nephron-protective effects against gentamicin-induced toxicity, mainly through antioxidant and anti-inflammatory mechanisms.