Renoprotective effect of vildagliptin following hepatic ischemia/reperfusion injury

Abstract

Remote renal injury is a drastic consequence of hepatic ischemia/reperfusion (IR) injury. Vildagliptin (V) is a dipeptidyl peptidase-4 inhibitor that has a hepatorenal protective effect against models of liver and renal IR. This research was done to explore the protective role of vildagliptin against renal injury following hepatic IR injury as well as the possible involvement of transforming growth factor-beta (TGF-b)/Smad/alpha-smooth muscle actin (a-SMA) expressions in the pathophysiological mechanism of the remote renal injury. Three groups of male Wistar rats were organized into: sham group, IR group, and V þ IR group in which 10 mg/kg/day of vildagliptin was pretreated for 10 days intraperitoneally. Blood in addition to renal and hepatic tissue samples was used for biochemical and histopathological studies. Hepatic IR induced a marked increase in serum creatinine, blood urea nitrogen, liver enzymes, renal nitric oxide, malondialdehyde, tumor necrosis factor-alpha levels with a marked upregulation of renal mRNA expressions of TGF-b, Smad2, Smad3, and a-SMA in addition to a marked decline in renal catalase content comparing to the sham group. Abnormal histopathological findings of hepatic and renal injury were detected in the IR group. Vildagliptin significantly improved these biochemical markers as well as the histopathological changes. The upregulation of renal TGF-b/Smad/a-SMA mRNA expressions was involved for the first time in the pathogenesis of the renal injury following hepatic IR and vildagliptin ameliorated this renal injury through blocking these expressions.

Effect of silibinin on the expression of MMP2, MMP3, MMP9 and TIMP2 in kidney and lung after hepatic ischemia/reperfusion injury in an experimental rat model

“…Sherif et al . 56 found that vildagliptin ameliorated the remote renal injury that occurred after hepatic IRI by reducing the oxidative stress and the pro-inflammatory cytokine TNF-a. Meng et al .…”

Combined saline and vildagliptin induced M2 macrophage polarization in hepatic injury induced by acute kidney injury

“…Group IV (AKI + vildagliptin): Treatment with daily oral vildagliptin 10 mg/kg (Galvus; Novartis Pharma Stein AG, Stein, Switzerland) ( Sherif, Alshaalan & Al-Shaalan, 2020 ) started 1 h after glycerol injection and continued with the same dose every 24 h for 72 h.…”

Vitamin D3 potentiates the nephroprotective effects of vildagliptin–metformin combination in a rat model of metabolic syndrome

“…The nephroprotective effect of the dipeptidyl peptidase-4 (DPP-4) inhibitors including vildagliptin has been attributed to the increased level of glucagon-like peptide-1 (GLP-1) resulting in antioxidant, antiinflammatory, antifibrotic, and antiapoptotic effects [6]. Metformin has also been shown to exert positive impact on the kidney both in vitro and in animal models, representing different types of renal diseases from acute kidney injury to CKD [7].…”