Reno-protective effect of linagliptin against gentamycin nephrotoxicity in rats

Background: Recent studies demonstrated the reno-protective effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, saxagliptin and sitagliptin, against gentamycin-induced renal injury. However, none of these studies investigated whether renal DPP-4 contributes to the pathogenesis of this nephrotoxicity or not. This prompted us to test this hypothesis and to assess, for the first time, the potential reno-protective effect of linagliptin and whether this action is related or not to DPP-4 inhibition. Lingliptin was chosen since it is mainly excreted through a non-renal pathway and can therefore be used safely in individuals with renal injury. Methods: Male Sprague-Dawley rats were administered gentamycin (100 mg/kg/day, ip for 10 days) alone or combined with linagliptin (3 mg/kg/day, orally for 14 days). Gentamycin was administered once daily during the last ten days of the linagliptin treatment. Results: Linagliptin administration ameliorated gentamycin-induced renal injury and restored renal functional, oxidative, inflammatory, apoptotic and histopathological changes. Furthermore, the current study highlighted the role of increased plasma and renal DPP-4 in the pathogenesis of gentamycin renal insults and showed that the potential reno-protective effect of linagliptin is partly, mediated via inhibition of DPP-4, in addition to other antioxidant, anti-inflammatory and antiapoptotic actions. Conclusion: Linagliptin may serve as a beneficial adjutant to reduce gentamycin-induced renal injury. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.