Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion

Abstract

Purpose Ischemia/reperfusion (IR) is the main cause of liver damage after transplantation. We evaluated the effect of sitagliptin (STG) on oxidative stress parameters in the rat liver under IR. Methods Rats were treated with STG (5 mg/kg) (S and SIR) or saline solution (C and CIR). Livers from CIR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). During reperfusion, aminotransferases (ALT and AST) were determined in blood samples. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), paraoxonase-1 (PON1), glutathione peroxidase (GPx), and the mRNA expression of SOD1 were determined in liver homogenates after reperfusion. Different regions of livers were also histologically evaluated. Results The PON1 activity was higher, and the TBARS level was lower in SIR than in CIR. There was an inverse relationship between TBARS and PON1 levels in the whole cohort. The GPx activity was lower in ischemic than in nonischemic groups regardless of the STG treatment. In SIR, the SOD1 activity was higher compared to that in CIR. In S, the expression of SOD1 mRNA was the highest of all examined groups and positively correlated with the SOD1 activity in the whole animal cohort. During IR aminotransferases, the activity in the drug-treated group was lower in all examined points of time. In drug-treated groups, the percentage of steatosis was higher than that in nontreated groups regardless of IR. Conclusions The protective effect of STG on the rat liver, especially its antioxidant properties, was revealed under IR conditions.

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

“…This is a follow-up study conducted on biobanked biological material collected during the original experiment [ 21 , 22 ]. Its design as well as the analytical methods used for the purpose of the current study are detailed below.…”

“…The presence of IR injury was confirmed by both the determination of the activity of aminotransferases during the reperfusion and the histological evaluation under a light microscope of different regions of ischemic and non-ischemic lobes of livers after IR procedure [ 22 ]. The activity of transaminases after reperfusion was the highest in the IR group.…”

“…The exception was a slight degree of necrosis and neutrophil infiltration in ischemic groups IR and SIR. The animals treated with sitagliptin (sitagliptin and SIR) showed a higher percentage of steatosis than the non-treated animals (control and IR) [ 22 ].…”

“…Several experimental studies have demonstrated pleiotropic properties, including the antioxidative, anti-inflammatory and antiapoptotic action of sitagliptin [ 18 , 19 ], a well-tolerated DPP-4 inhibitor with moderate side effects [ 20 ]. Accordingly, we [ 21 , 22 ], as well as others [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], have shown that sitagliptin alleviates injury caused by IR procedure. However, the molecular background has not been fully elucidated.…”

Oxidative stress markers in liver in streptozocin-induced diabetic rats: effects of metformin and sitagliptin

“…Sitagliptin suppresses glucagon secretion due to DDP-4 inhibition, thus stimulating the liver and decreasing glucose production. In some studies in recent years, STG has been reported to show antioxidative effects [14][15][16][17] . This study investigates the oxidative stress effects of metformin and sitagliptin in the liver in a type 2 diabetes mellitus rat model.…”