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2015 ; 7
(ä): 107
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DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart
and kidney in two kidney and one clip (2K1C) rats
#MMPMID26609328
Alam MA
; Chowdhury MRH
; Jain P
; Sagor MAT
; Reza HM
Diabetol Metab Syndr
2015[]; 7
(ä): 107
PMID26609328
show ga
BACKGROUND: 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. METHODS: Male 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. RESULTS: 2K1C 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. CONCLUSION: Our 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.