Abstract
BackgroundHyperglycemia and insulin resistance often develop cardiovascular and nephrological dysfunction in diabetic patients. Sitagliptin is used to treat diabetes and showed potential benefit in lowering increased blood glucose level in diabetes. This investigation reports the effect of sitagliptin treatment on oxidative stress in kidney and heart of 2K1C rats.MethodsMale Long Evans rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2K1C) method]. These animals entered a 4-weeks dosing period with sitagliptin. Blood and urine sampling and organ harvesting were finally performed. Blood plasma, heart, kidney tissues and urine were tested for the assessment of inflammation and oxidative stress in kidney and heart of 2K1C rats after 4 weeks of surgery.Results2K1C rats showed cardiac hypertrophy, increased left ventricular wet weight compared to sham which was not significantly altered by sitagliptin treatment. Uric acid and creatinin concentrations were also increased in 2K1C rats. Sitagliptin significantly prevented the elevation of uric acid and creatinin concentration in plasma and urine in this rat model. Oxidative stress markers in plasma such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) concentrations were increased in the 2K1C rats as compared to sham-operated animals. Increased concentrations of these oxidative stress markers were also normalized by sitagliptin treatment. 2K1C rats also showed increased level of uric acid and creatinine both in plasma and urine; which are also reduced to normal level in sitagliptin treated rats. Moreover, 2K1C surgery initiated inflammatory cell infiltration, increased MPO activity and fibrosis in both heart and kidneys which were further ameliorated by sitagliptin treatment.ConclusionOur study suggests that sitagliptin treatment in 2K1C rats prevented inflammation and fibrosis of heart and kidney by ameliorating elevated oxidative stress in heart and kidney tissues.
Highlights
Hyperglycemia and insulin resistance often develop cardiovascular and nephrological dysfunction in diabetic patients
Effect of sitagliptin on body weight, food and water intake in 2K1C rats Body weight of each rat was recorded every day during the experiment, and % change was calculated for all groups
It was found that the body weight increased consistently in sitagliptin treated rats group, which is denoted that the treatment have no effect on the body weight
Summary
Hyperglycemia and insulin resistance often develop cardiovascular and nephrological dysfunction in diabetic patients. Sitagliptin is used to treat diabetes and showed potential benefit in lowering increased blood glucose level in diabetes. This investigation reports the effect of sitagliptin treatment on oxidative stress in kidney and heart of 2K1C rats. Congestive heart failure and kidney dysfunction are major causes of mortality and morbidity in patient suffering diabetes worldwide [1, 2]. Several reports suggest that NADPH oxidase containing neutrophil infiltration in myocardium is mainly responsible for free radicals mediated oxidative stress in heart [9, 12]
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