Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects

Nephrotoxicity is a serious adverse effect frequently encountered with aminoglycosides administration. Given the value of aminoglycosides in management of serious infections, nephro-protection is highly recommended. The current study investigated the nephro-protective effect of saxagliptin (SAXA) (12.5 mg/kg, I.P.) against gentamicin (GEN)-induced nephrotoxicity in rats. SAXA administration for 14 days conferred significant nephro-protection against GEN-induced nephrotoxicity manifested in decreased kidney/somatic index, enhanced cytoprotection and significant decrease in serum LDH activity together with functional renal improvement; significant increase in creatinine clearance with significant reduction in serum creatinine, BUN, proteinuria and albuminuria. Oxidant/antioxidants hemostasis was significantly improved with SAXA treatment with significant reduction in kidney MDA content and enhancement of GSH concentration and catalase activity. Moreover, kidney content of NO significantly declined with significant decline in kidney tumor necrosis factorα (TNFα), vascular adhesion molecule-1 (VCAM-1) and caspase-3 content. Ultimately, SAXA administration was associated with significant attenuation of GEN-induced necrotic and inflammatory changes. In conclusion; the modulatory effect of SAXA on inflammatory cytokines, its anti-apoptic properties, ameliorative impact on oxidative load and positive impact on host antioxidant defenses accounts for the observed nephro-protective impact.