Vol. 85, March 2017

Effect of Myriocin on Atherosclerosis Induced by High Fat High Cholesterol Diet in Rats

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Effect of Myriocin on Atherosclerosis Induced by High Fat High Cholesterol Diet in Rats, NAHID M. TAHOON, DOAA H. ZINELDEEN, RABAB M. AMER and KARIMA EL-DESUKY

 

 Abstract
Background: Altered sphingolipid (SpL) levels, particularly ceramide (Cer) and sphingomyelin (SM), are involved in obesity-induced endothelial dysfunction and atherosclerosis (AS).
Aim: This study aimed at examining the role of inhibition of serine palmitoyl transferase (SPT) by myriocin as a thera-peutic candidate for atherosclerosis model induced by 12 weeks high fat high cholesterol diet (HFHCD) in rats.
Material and Methods: This study was carried out on 30 male wistar rats of local strain which were divided into 3 equal groups. Gr I: Standard diet (SD) fed rats as a control group. Gr II: High fat high cholesterol diet (HFHCD) fed rats. Gr III: HFHCD fed rats treated with myriocin. At the end of the experimental period (12 weeks), lipid profile (LDL-ch, HDL-ch, TG, TC, ox-LDL and plasma ceramide), oxidative, inflammatory and endothelial markers [reduced glutathione (GSH), C-reactive protein (CRP) and total serum nitrite / nitrate (NOx)] were measured. Correlation was done between ceramide and lipid parameters (HDL-ch, TC and ox-LDL). Histopathological examination of tissue samples from aortae and coronaries was done in all groups.
Results: HFHCD produced significant dyslipidemia, in-creased CRP, decreased GSH and NOx. Cer levels negatively correlated with HDL-ch and positively correlated with TC and ox-LDL. Atherosclerotic changes were evident by histopatho-logical examination (foam cells and vascular smooth muscle cell proliferation). Myriocin succeeded to significantly reverse biochemical and histological results induced by HFHCD.
Conclusion: Myriocin inhibits development and progres-sion of AS via multiple diverse chemical scinarios including suppression of de novo lipogenesis, enhancing HDL-biogenesis, function and turnover, and improving endothelial dysfunction.

 

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