Targeting lipoxygenase Enzyme As A possible Therapeutic Srtategy For Treatment Of Diabetic Atherosclerosis

In this work, the potential protective effect of lipoxygenase isozymes (LOXs) inhibitors on diabetic macrovascular complications (the first stage in diabetic atherosclerosis) was studied.Initially we induced two experimental models; Insulin deficiency (ID) model induced by streptozotocin injection and insulin resistance (IR) model induced by fructose administration. Both of which were accompanied with vascular complications.The effect of LOXs inhibitors; quercetin, baicalein and caffeic acid phenethyl ester (CAPE) during development of vascular complications associated with ID and IR was fully investigated. The systolic blood pressure (BP), diastolic BP and pulse pressure were recorded. Vascular reactivity to standard vasoconstrictors; phenylephrine and KCl and vasodilator; ACh was examined using the isolated artery technique.The structural alterations of the vascular system associated with diabetes were determined by histopathological examination of isolated aorta to investigate endothelial pyknosis and leukocyte infiltration. In addition the extent of collagen deposition was estimated to determine the level of vessel wall stiffness.In order to elucidate the possible mechanisms that explain our results, serum levels of glucose, insulin, advanced glycation endproducts (AGEs) and tumor necrosis factor-α (TNF-α) were also measured. In addition, the expression of heme oxygenase-1 (HO-1) enzyme and the activation of nuclear factor kappa B (NFκ-B) in the isolated aorta sections were determined by immunofluorescence techniques.