title: 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.
authors.affiliation: Division of Pharmacology, Central Drug Research Institute, 1. M.G. Marg, Lucknow, UP 226001, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Singh
authors.forename: Manish
authors.initials: M
authors.lastname: Jain
authors.forename: Prem
authors.initials: P
authors.lastname: Prakash
authors.forename: Ankita
authors.initials: A
authors.lastname: Misra
authors.forename: Vivek
authors.initials: V
authors.lastname: Khanna
authors.forename: Rajiv Lochan
authors.initials: RL
authors.lastname: Tiwari
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Keshari
authors.forename: Shivendra
authors.initials: S
authors.lastname: Singh
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Barthwal
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D010976:Platelet Count; D013927:Thrombosis / Q000139:chemically induced; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha