Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats

Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS) were assessed. After 60？days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. In the STZ？+？HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group.There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. In the STZ？+？HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. In conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant activity of HO-1.Diabetic nephropathy is one of the most serious complications of diabetes and the most common cause of end-stage renal failure. At present, diabetic kidney disease affects about 15%–25% of type I diabetes patients [1] and 30%–40% of patients with type II diabetes [2]. Diabetic nephropathy is characterized by specific renal morphological and functional alterations.According to clinical studies, the comorbidities of hypertension, glucose intolerance, and insulin resistance are considered the major contributors to the development of metabolic syndrome and diabetes [3-5].Reactive oxygen species (ROS) play an important role in diabetes and its complications [6,7]. Experimental studies demonstrated the involvement of ROS in