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

Vishal Singh, Manish Jain, Prem Prakash, Ankita Misra, Vivek Khanna, Rajiv Lochan Tiwari, Ravi Shankar Keshari, Shivendra Singh, Madhu Dikshit, Manoj Kumar Barthwal

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 chlorideinduced 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.

Original languageEnglish (US)
Pages (from-to)205-216
Number of pages12
JournalJournal of Physiology and Biochemistry
Volume67
Issue number2
DOIs
StatePublished - Jun 1 2011

Fingerprint

Time and motion study
Platelets
Cricetinae
Blood Platelets
Cholesterol
Modulation
Pharmaceutical Preparations
Nutrition
clopidogrel
Platelet Activation
Diet
Thrombin
Thrombosis
Collagen
Adhesion
Agglomeration
Chemical activation
Thrombin Time
Chronology
Lipids

All Science Journal Classification (ASJC) codes

  • Physiology
  • Biochemistry

Cite this

Singh, Vishal ; Jain, Manish ; Prakash, Prem ; Misra, Ankita ; Khanna, Vivek ; Tiwari, Rajiv Lochan ; Keshari, Ravi Shankar ; Singh, Shivendra ; Dikshit, Madhu ; Barthwal, Manoj Kumar. / A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters. In: Journal of Physiology and Biochemistry. 2011 ; Vol. 67, No. 2. pp. 205-216.
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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 chlorideinduced 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.",
author = "Vishal Singh and Manish Jain and Prem Prakash and Ankita Misra and Vivek Khanna and Tiwari, {Rajiv Lochan} and Keshari, {Ravi Shankar} and Shivendra Singh and Madhu Dikshit and Barthwal, {Manoj Kumar}",
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Singh, V, Jain, M, Prakash, P, Misra, A, Khanna, V, Tiwari, RL, Keshari, RS, Singh, S, Dikshit, M & Barthwal, MK 2011, 'A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters', Journal of Physiology and Biochemistry, vol. 67, no. 2, pp. 205-216. https://doi.org/10.1007/s13105-010-0065-z

A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters. / Singh, Vishal; Jain, Manish; Prakash, Prem; Misra, Ankita; Khanna, Vivek; Tiwari, Rajiv Lochan; Keshari, Ravi Shankar; Singh, Shivendra; Dikshit, Madhu; Barthwal, Manoj Kumar.

In: Journal of Physiology and Biochemistry, Vol. 67, No. 2, 01.06.2011, p. 205-216.

Research output: Contribution to journalArticle

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T1 - A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters

AU - Singh, Vishal

AU - Jain, Manish

AU - Prakash, Prem

AU - Misra, Ankita

AU - Khanna, Vivek

AU - Tiwari, Rajiv Lochan

AU - Keshari, Ravi Shankar

AU - Singh, Shivendra

AU - Dikshit, Madhu

AU - Barthwal, Manoj Kumar

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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 chlorideinduced 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.

AB - 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 chlorideinduced 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.

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