Renoprotective action of rabeprazole and lansoprazole in gentamicin-induced nephrotoxicity: roles of oxidative stress, apoptosis, ER stress, and OCT2 expression

Abstract Background Gentamicin (GNT)-induced nephrotoxicity involves oxidative stress, apoptosis, and enhanced renal accumulation, partly mediated by OCT2 transport activity. Proton pump inhibitors (PPIs) have been reported to exhibit nephroprotective actions beyond their gastric acid–suppressive effects. Accordingly, this study investigates the nephroprotective effects of rabeprazole (Rabe) and lansoprazole (Lanso) against GNT-induced nephrotoxicity in rats and explores their potential underlying mechanisms with particular focus on oxidative stress modulation, apoptotic signaling, endoplasmic reticulum (ER) stress regulation, and OCT2 expression. Rats were randomized into six groups: a saline control, a GNT group (100 mg/kg, ip/ eight days), two groups receiving Rabe or Lanso alone (20 mg/kg, orally / eight days), and two groups receiving Rabe or Lanso one hour before GNT for eight days. On day nine, blood and kidney tissues were collected for biochemical, molecular, and histopathological assessment. Results Both PPIs improved renal function parameters, mitigated oxidative stress, and favorably influenced key apoptotic markers. They also attenuated ER stress indicators and modulated OCT2 expression, suggesting a potential role in limiting GNT-induced renal accumulation. Histopathological evaluation further supported these biochemical findings, showing noticeable preservation of renal tubular structure in PPI-treated rats. Both agents demonstrated nephroprotective effects in the current experimental setting; however, Lanso exhibited comparatively greater improvement in several evaluated parameters. Conclusions Our findings indicate that Rabe and Lanso may have promising nephroprotective potential against GNT-induced renal injury and warrant further preclinical validation and subsequent clinical assessment.