A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters

Abstract

The present study was undertaken to assess the chronology of major pathological events associated with high cholesterol (HC) diet and their modulation by anti-platelet drugs. Male Golden Syrian hamsters were fed HC diet up to 90 days. Plasma lipid, glucose and coagulation parameters (commercial kits), platelet activation (whole blood aggregation and static adhesion), endothelial dysfunction (aortic ring vasoreactivity), splenocyte TNF-α, IFN-γ and iNOS mRNA transcripts (RT-PCR), and ferric chloride (time to occlusion) induced thrombosis were monitored at 15, 30, 60, and 90 days after HC feeding and compared with normolipidemic hamsters. A significant increase in plasma lipid levels was observed at 15 days of HC feeding, but other parameters remain unaltered. Enhanced ADP, collagen, and thrombin-induced platelet aggregation, splenocyte TNF-α expression along with endothelial dysfunction were observed from 30 to 90 days of HC feeding. Platelet adhesion on collagen-/fibrinogen-coated surface and IFN-γ expression were augmented only after 60 days, while enhanced iNOS expression, reduction in thrombin time, and potentiation of ferric chloride-induced thrombosis was observed only at 90 days of HC feeding. Thus, pathological changes induced by HC diet depend on the duration and extent of hyperlipidemia. Moreover, hamsters treated with anti-platelet drugs aspirin (5 mg/kg) or clopidogrel (10 mg/kg) along with HC feeding exhibited reduction in platelet activation as well as subsequent changes observed in the abovementioned parameters following HC feeding. Since reduction in TNF-α was associated with reversion in endothelial dysfunction and prothrombotic state, the role of platelets is implicated in the pathological changes associated with HC feeding.

Curcuma Oil Reduces Endothelial Cell-mediated Inflammation in Postmyocardial Ischemia/Reperfusion in Rats

“…Ring viability and maximum contraction were assessed by 80 mM KCl. 20,21 Enzyme-linked Immunosorbent Assay Enzyme-linked immunosorbent assay was performed on plasma samples collected on the last day of the experiment. Blood was withdrawn through cardiac puncture in a plastic syringe supplemented with 1.9% of trisodium citrate.…”

Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats

“…After 1 week, the animals were randomly distributed in two groups: the first group received normal chow diet and the other received high fructose diet (HFr) containing 35% fructose, 5% saturated fat (coconut oil), essential vitamins and minerals along with 25% fructose in drinking water. Normal chow and high fructose diet were prepared at the CDRI diet production facility using various components as listed in Table 1 [20]. After 10 weeks of feeding, the HFr group was further split in two groups, the first group received atorvastatin (ATV; 30 mg/kg/day; per oral) and the second group was kept on vehicle [aqueous carboxymethylcellulose (CMC) suspension] for two additional weeks.…”

Coconut Oil and Cholesterol as Challenge Agents to Induce Hyperlipidemia and Atherosclerosis in Hamster Animal Model

“…In 2011, Singh and colleagues reported a significant development of hyperlipidemia in HFHC fed hamster compared to normal control and baseline result. However, the lipoprotein profile for TC, TG, and LDL-c started to decrease slightly after 30 days of diet challenge (Singh et al 2011).…”

“…Not many previous studies were found using this amount of cholesterol in the combination of CNO as the fat source. As illustrated in Table 3, the amount of dietary cholesterol supplemented into the diet were in the range of 3-5% together with the addition of 15% CNO (Mangiapane et al 1999;Mcateer et al 2007;Singh et al 2011). On the other hand, there are also studies which are conducted with the dietary design of more than 1.0% cholesterol in the combination of another type of dietary fat such as butter (de Oliveira et al 2000;Sima et al 2001;Simionescu et al 1996;Stancu et al 2014) and lard (Zhao et al 2014).…”