Antiatherosclerotic potential of clopidogrel: antioxidant and anti-inflammatory approaches.
BACKGROUND
Atherosclerosis is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the walls of large and medium size arteries.


OBJECTIVE
To evaluate the effect of clopidogrel on atherosclerosis progression.


METHODS
A total of 28 local domestic rabbits were assigned to four groups: normal control, atherogenic control, vehicle control, and clopidogrel treated. Serum triglycerides, total cholesterol, HDL-C, plasma high sensitive C-reactive protein (hsCRP), plasma malondialdehyde (MDA), and plasma reduced glutathione (GSH) were measured at the end of the experiment. Immunohistochemical of aortic atherosclerotic changes were also performed.


RESULTS
There was no statistically significant difference between atherogenic control group and vehicle group. Levels of lipid profile, atherogenic index, hsCRP, and MDA are increased while GSH levels were decreased in animals on atherogenic diet. Immunohistochemical analysis showed that aortic expressions of VCAM-1, MCP-1, TNF- α , and IL-17A were significantly increased in atherogenic control group. Histopathologic finding showed that animals on atherogenic diet have significant atherosclerotic lesion. Compared to atherogenic control group clopidogrel do not have significant effect on lipid profile. Clopidogrel significantly reduces hsCRP and MDA levels and increases GSH level. Furthermore, clopidogrel treatment significantly reduced aortic expressions parameters and the histopathologic examination of the aortic arch showed a significant reduction of atherosclerotic lesion.


CONCLUSIONS
This study outlines how clopidogrel reduces lipid peroxidation, systemic inflammation, and aortic expression of inflammatory markers and hence reduces the progression of atherosclerosis.
Department of Pharmacology, College Medicine, University of Kufa, Najaf, Iraq.
Najah R
NR
Hadi
College of Pharmacy, University of Al-Qadissiya, Diwaniya, Iraq.
Bassim I
BI
Mohammad
Department of Physiology, College Medicine, University of Kufa, Najaf, Iraq.
Ihsan M
IM
Ajeena
Department of Pharmacology, College Medicine, University of Kufa, Najaf, Iraq.
Hussam H
HH
Sahib
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D000077144:Clopidogrel; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D011817:Rabbits; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018932:Chemokine CCL2; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000077144:Clopidogrel; D013988:Ticlopidine