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Original Article

JCDR. 2017; 8(2): 50-55

Lowering Inflammation Level by Lp-PLA2 Inhibitor (Darapladib) in Early Atherosclerosis Development: in vivo Rat Type 2 Diabetes Mellitus Model

Heriansyah Teuku, Wihastuti Titin Andri, Bambang Budi Siswanto,Anwar Santoso, Renan Sukmawan, Djanggan Sargowo, Imam Subekti, Aulanni’am, Nurjati Chairani Siregar,Saptawati Bordosono.


Background: Type 2 Diabetes Melitus (T2DM) is a condition of insulin resistance that causes extensive tissue damage
due to vascular inflammation and oxidative stress. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has anti-inflammatory
role as it hydrolyzes atherogenesis mediators such as oxidized LDL (Ox LDL) and platelet activating factor (PAF)
but in contrast, it has pro inflammatory effect as it produced lysophosphatidylcholine (lysoPC) and oxidized fatty acid
(oxFA). Methods and Results: This study aimed to measure inflammation marker of T2DM in vivo model with Lp-PLA2
selective inhibitor (darapladib) treatment. It used true experimental laboratory and post test only with control group design
using 30 spraque dowley rats that is divided into 3 main groups: normal, T2DM, and T2DM with darapladib (DMDP)
administration group. Each group are divided into 2 serial treatment times: 8-weeks and 16-weeks intervention. So, there
are 6 groups total with 5 rat in each group. Parameter measured was ox-LDL, tumor necrosis factor-α (TNF-α), inducible
nitric oxide synthase (iNOS), interleukin 6 (IL-6), PAF, perivascular adipose tissue (PAT) thickness and also blood glucose,
lipid profile, and insulin plasma level. ANOVA test result showed that darapladib were significantly (p: 0.000) lowering
tissue and blood ox-LDL level, iNOS, PAF, IL-6 and PAT thickness on T2DM in vivo model. Conclusions: Darapladib proved
to have anti inflammation role on T2DM model.

Key words: Type 2 diabetes mellitus, Inflammation, Oxidative stress, Lipoprotein-associated phospholipase A2, Darapladib

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