title: Caffeic acid phenethyl ester, a 5-lipoxygenase enzyme inhibitor, alleviates diabetic atherosclerotic manifestations: effect on vascular reactivity and stiffness.
abstract: Atherosclerosis is a major macrovascular complication of diabetes that increases the risks for myocardial infarction, stroke, and other vascular diseases. The effect of a selective 5-lipoxygenase enzyme inhibitor; caffeic acid phenethyl ester (CAPE) on diabetes-induced atherosclerotic manifestations was investigated. Insulin deficiency or resistance was induced by STZ or fructose respectively. Atherosclerosis developed when rats were left for 8 or 12 weeks subsequent STZ or fructose administration respectively. CAPE (30 mg kg(-1) day(-1)) was given in the last 6 weeks. Afterwards, blood pressure (BP) was recorded. Then, isolated aorta reactivity to KCl and phenylephrine (PE) was studied. Blood glucose level, serum levels of insulin, tumor necrosis factor α (TNF-α) as well as advanced glycation end products (AGEs) were determined. Moreover aortic haem oxygenase-1 (HO-1) protein expression and collagen deposition were also assessed. Insulin deficiency and resistance were accompanied with elevated BP, exaggerated response to KCl and PE, elevated serum TNF-α and AGEs levels. Both models showed marked increase in collagen deposition. However, CAPE alleviated systolic and diastolic BP elevations and the exaggerated vascular contractility to both PE and KCl in both models without affecting AGEs level. CAPE inhibited TNF-α serum level elevation, induced aortic HO-1 expression and reduced collagen deposition. CAPE prevented development of hyperinsulinemia in insulin resistance model without any impact on the developed hyperglycemia in insulin deficiency model. In conclusion, CAPE offsets the atherosclerotic changes associated with diabetes via amelioration of the significant functional and structural derangements in the vessels in addition to its antihyperinsulinemic effect in insulin resistant model.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt.
authors: Noura Ahmed
authors: NA
authors: Hassan
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Saudi Arabia. Electronic address: helbassossy@zu.edu.eg.
authors: Hany M
authors: HM
authors: El-Bassossy
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt.
authors: Mona Fouad
authors: MF
authors: Mahmoud
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt.
authors: Ahmed
authors: A
authors: Fahmy
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects*; D050197:Atherosclerosis / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D048909:Diabetes Complications / Q000188:drug therapy; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D059289:Vascular Stiffness / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002109:Caffeic Acids; D007328:Insulin; D016859:Lipoxygenase Inhibitors; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Aorta; Atherosclerosis; Caffeic acid phenethyl ester; Diabetes; Vascular reactivity