eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-12-30 18 4 3138 3153 10.13005/bpj/3323 68814 article Kajal Pansare 1 Yogesh Ahire 1 Vinod Bairagi 1 Department of Pharmacology, Savitribai Phule Pune University Affiliated, KBHSS Trusts Institute of Pharmacy, Malegaon, Nashik, India Gentamicin, historically widely used and still employed in specific clinical settings, often causes nephrotoxicity primarily through oxidative stress and inflammation, among other mechanisms. This study evaluates the protective effect of Naringenin, a flavonoid antioxidant, and Bromelain, an anti-inflammatory proteolytic enzyme, against gentamicin-induced renal injury in male Wistar rats. Animals were divided into eight groups, including normal and gentamicin controls, standard treatment (N-acetyl cysteine), varying doses of Naringenin and Bromelain, and their combination. Nephrotoxicity was induced with gentamicin (80 mg/kg/day, i.p., for 8 days). Parameters such as body/kidney weight, urine output, biochemical markers, oxidative stress indicators, cytokines, and histopathology were assessed. Gentamicin caused significant renal damage, evidenced by increased serum urea (51.27 ± 6.10 mg/dL) and creatinine (6.13 ± 1.37 mg/dL) compared to control (p < 0.001). Treatment with Naringenin (20 mg/kg) and Bromelain (30 mg/kg) significantly reduced serum creatinine to 3.80 ± 0.71 mg/dL and 4.06 ± 0.58 mg/dL, respectively (p < 0.01 vs. gentamicin). The combination therapy produced the most pronounced effect, lowering serum creatinine to 2.85 ± 0.59 mg/dL and restoring total protein levels by nearly 90% compared to the control group (p < 0.001). Histopathological analysis further confirmed marked recovery of renal architecture, with the combination group showing minimal inflammatory infiltration and near-normal morphology. Overall, the combination therapy showed statistically significant (p < 0.001) superior nephroprotection compared to individual treatments, highlighting its potential as a natural, synergistic alternative for mitigating drug-induced nephrotoxicity. https://biomedpharmajournal.org/vol18no4/a-novel-combination-approach-using-naringenin-and-bromelain/ Bromelain Combination therapy Gentamicin N-acetyl cysteine Naringenin Nephropathy Nephroprotective agents Oxidative stress