Targeting Heme Oxygenase-1 Enzyme As A possible Therapeutic Strategy For Treatment Of Diabetic Vascular Compl-ications

In this work, the role of HO-1 enzyme stimulation in diabetic macrovascular dysfunction (the first stage in diabetic atherosclerosis) was studied.Initially we induced two experimental models in rats; diabetic model (by STZ injection) and IR model (by fructose administration). Both of which were accompanied with vascular complications. HO-1 was induced by intraperitoneal injection of curcumin (5 mg/kg) or hemin (10 mg/kg) to rats during developments of vascular complications.Inductionof HO-1 expression was determined by immunofluorescence technique. The effect of HO-1 inductionon the development of vascular complications associated with diabetes and IR was fully investigated; the systolic BP and diastolic BP were recorded. Vascular reactivity to standard vasoconstrictors; PE and KCl and vasodilator; ACh were examined using the isolated artery technique. Serum levels of glucose, insulin, TNF-α and AGEs were also determined. In addition, the aortic ROSgeneration was determined as well as ACh stimulated NO generation from the endothelium. To confirm the role of HO -1 enzyme stimulation in the seen vascular protection, aorta isolated from hemin treated animals were incubated with the HO inhibitor, SNPP then the vascular reactivity was examined using the isolated artery technique.