Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

• Published in: Endocrine regulations (Bratislava) 2018-04, Vol.52 (2), p.69-75
• Main Authors: Wihastuti, Titin Andri, Heriansyah, Teuku, Hanifa, Hanifa, Andarini, Sri, Sholichah, Zuhrotus, Sulfia, Yuni Hendrati, Adam, Aditya Angela, Refialdinata, Jeki, Lutfiana, Nurul Cholifah
• Format: Article
• Language: English
• Subjects: Animals; Aorta - drug effects; Aorta - metabolism; atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Benzaldehydes - administration & dosage; Benzaldehydes - pharmacology; darapladib; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diet, High-Fat; Oximes - administration & dosage; Oximes - pharmacology; Phospholipase A2 Inhibitors - administration & dosage; Phospholipase A2 Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; type 2 diabetes mellitus rat model
• ISSN: 1210-0668; 1336-0329; 1336-0329
• DOI: 10.2478/enr-2018-0008

Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p