Role of selenium in cytoprotection against cholesterol oxide-induced vascular damage in rats.
Wistar rats were fed Se-deficient (0.038 mg/kg diet) and adequate (0.326 mg/kg diet) diets for 13 weeks. The blood Se content, blood and vascular wall glutathione peroxidase (GPx) activity, serum high-density lipoprotein cholesterol (HDL-C) level and plasma prostacyclin (PGI(2)) concentration were decreased significantly, and the blood lipid peroxide (LPO) concentration, serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) level and plasma thromboxane A(2) (TXA(2)), content were increased significantly in Se-deficient rats compared with Se-adequate group, respectively. Furthermore the Se-deficient and adequate rats were given 5 mg/kg of cholestane-3 beta, 5 alpha, 6 beta -triol (3-triol) or vehicle only. Twenty four hours after treatment, the plasma PGI(2) level was decreased in Se-adequate rats infused 3-triol (+3 triol), meanwhile, the level in Se- deficient +3-triol group was much lower than that in Se-adequate +3-triol group. Compared with Se-adequate group, plasma TXA(2) content in Se-adequate +3-triol group had no significantly difference, but in Se- deficient rats infused 3-triol, plasma TXA(2) content was much higher than that in Se-adequate +3-triol group. The plasma ET concentration in Se-deficient group decreased slightly, but the concentration in Se-adequate +3-triol group increased significantly with respect to Se-deficient group. Although plasma ET concentration in Se-deficient group +3-triol did not increase, it was significantly lower than that in Se-adequate +3-triol group. The luminal surfaces of aorta thoracica of experimental rats were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Observed by SEM, the luminal surface of aorta of Se-deficient rats showed few crater-like defects due to the disruption of endothelial cell. Se-adequate +3-triol group showed some crater-like defects on the their aorta luminal surface, but the luminal surface of Se-deficient +3-triol group exhibited numerous crater-like defects and appeared sponge-like as well as platelets adhering followed by thrombus formation in focal area of extensive endothelial damage. TEM studies also showed that the endothelium of aorta of Se deficient +3-triol group had more frequent lesion where endothelial cell plasma were swelling with profuse intracellular edema and some vacuoles were seen in cytoplasm. In severely injured areas, endothelial integrity was completely destroyed and smooth muscle cells were proliferating and migrated to the endomembrane. Thus, we can conclude that Se or selenoproteins in the vascular wall plays an important role in cytoprotection against cholesterol oxide-induced vascular damage in rats.
Huang
Kaixun
K
Department of Chemistry, Huazhong University of Science and Technology, Wuhan, Hubei 430074, People's Republic of China. wkx1954@public.wh.hb.cn
Liu
Hongmei
H
Chen
Zexian
Z
Xu
Huibi
H
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001011:Aorta / Q000737:chemistry; D002777:Cholestanols / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004195:Disease Models, Animal; D016232:Endothelins / Q000097:blood / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008054:Lipid Peroxides / Q000097:blood; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000494:pharmacology* / Q000502:physiology*; D013929:Thromboxane B2 / Q000097:blood; D014280:Triglycerides / Q000097:blood
D002777:Cholestanols; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D016232:Endothelins; D000960:Hypolipidemic Agents; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; C000474:cholestane-3,5,6-triol; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005979:Glutathione Peroxidase; D012643:Selenium