tin-mesoporphyrin and Hyperglycemia

Heme oxygenase-1 (HO-1) represents a key defense mechanism against oxidative injury. Hyperglycemia has been linked to increased oxidative stress, leading to endothelial dysfunction, delayed cell replication, and enhanced apoptosis. The effect of streptozotocin (STZ)-induced diabetes on HO activity, HO-1 promoter activity, superoxide anion (O*-2, and the number of circulating endothelial cells was measured. The expression of HO-1/HO-2 protein was unchanged, but HO activity was decreased in aortas of diabetic rats compared with control (p < 0.05). High glucose decreased HO-1 promoter activity (p < 0.05). Hyperglycemia increased O*-2 and this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation (p < 0.05). Circulating endothelial cells were significantly higher in diabetic rats and were decreased or increased with administration of the HO-1 inducer (CoPP) or inhibitor (SnMP), respectively (p<0.05). In conclusion, HO-1 upregulation in diabetic rats brings about an increase in serum bilirubin, a reduction in O*-2 production, and a decrease in endothelial cell sloughing.

Topics: Animals; Anions; Antineoplastic Combined Chemotherapy Protocols; Aorta; Apoptosis; Bilirubin; Blotting, Western; Cells, Cultured; Cyclophosphamide; Diabetes Mellitus, Experimental; Endothelial Cells; Endothelium, Vascular; Enzyme Inhibitors; Glucose; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hyperglycemia; Luciferases; Male; Metalloporphyrins; Oxidative Stress; Oxygen; Plasmids; Prednisone; Procarbazine; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Streptozocin; Superoxides; Time Factors; Transfection; Up-Regulation; Vincristine