26 research outputs found
Protein Kinase C Plays an Important Role in Exaggerated Vasoconstriction Associated with Insulin Deficiency but not Resistance
Characterization of vascular complications in experimental model of fructose-induced metabolic syndrome
Zingerone alleviates the delayed ventricular repolarization and AV conduction in diabetes: Effect on cardiac fibrosis and inflammation
PARP inhibition ameliorates nephropathy in an animal model of type 2 diabetes: focus on oxidative stress, inflammation, and fibrosis
Poly(ADP-ribose) polymerase (PARP) enzyme
contributes to nephropathy, a serious diabetic complication
which may lead to end-stage renal disease. The study aims
to investigate the effect of PARP over-activation on kidney
functions in a type 2 diabetic rat model. The study also tests
the therapeutic use of PARP inhibitors in diabetic nephropathy.
Type 2 diabetes was induced in adult male rats by highfructose/high-fat
diet and low streptozotocin dose. Then, the
PARP inhibitor 4-aminobenzamide (4-AB) was administered
daily for 10 weeks. At the end, urine samples were collected to
measure urine creatinine, albumin, and total proteins. PARP
activity, superoxide dismutase (SOD) activity, and nitrite content
were measured in kidney tissue homogenate. Glucose,
fructosamine, insulin, and tumor necrosis factor-alpha
(TNF-α) were measured in serum. Furthermore, histological
studies, collagen deposition, and immunofluorescence of nuclear
factor kappa B (NFÎșB) and transforming growth factor
beta1 (TGF-ÎČ1) were carried out. PARP enzyme activity was
significantly higher in the diabetic group and was significantly
reduced by 4-AB administration. Diabetic animals had clear
nephropathy indicated by proteinuria and increased albumin
excretion rate (AER) which were significantly decreased by
PARP inhibition. In addition, PARP inhibition increased creatinine
clearance in diabetic animals and reduced renal
TGF-ÎČ1 and glomerular fibrosis. Moreover, PARP inhibition
alleviated the elevated serum TNF-α level, renal NFÎșB, nitrite,
and the decrease in SOD activity in diabetic animals.
However, PARP inhibition did not significantly affect neither
hyperglycemia nor insulin sensitivity. PARP enzyme inhibition
alleviates diabetic nephropathy through decreasing inflammation,
oxidative stress, and renal fibrosi