[Effect of NIP-200 on hyperlipidemia and atherosclerosis in cholesterol-fed rabbits].
The hypolipidemic and antiatherosclerotic effects of NIP-200 (3,5-dimethyl-4,6-diphenyl-tetrahydro-2H-1,3,5-thiadiazine-2-th ion e) were studied in experimental models of 1% cholesterol diet (HCD)-fed rabbits. The increases of total lipids, total cholesterol (TC), free cholesterol (FC) and phospholipid (PL) in plasma by HCD-feeding were inhibited by the treatment of NIP-200. The plasma contents of TC in high density lipoprotein (HDL-TC) and HDL-PL in the treatment of NIP-200 were increased more than that of the control and the HCD-fed group, but the former was not significantly different compared to the HCD-fed group. Both atherogenic index using TC-HDL-TC/HDL-TC and PL-HDL-PL/HDL-PL were reduced by NIP-200. There was a slight deposition of fatty plaques on the lumen surface of the thoracic aorta in the HCD-fed and NIP-200-treated rabbits. In the scanning electron microscopic study on the lumen surface of the aortic arch, NIP-200 reduced fatty plaques. NIP-200 also prevented the loss of endothelial fissures and swelling of the nuclei. It is suggested that the hypolipidemic action of NIP-200 may be the inhibition of lipid absorption in the intestine and the acceleration of lipid excretion in the liver. The antiatherosclerotic action of NIP-200 may be due to the improvement of lipid metabolism by the increases of HDL-TC and HDL-PL in plasma.
Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
K
K
Sakamoto
M
M
Yamauchi
S
S
Nakayama
N
N
Tsuruzoe
M
M
Sakashita
Y
Y
Fujikawa
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007408:Intestinal Absorption; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D011817:Rabbits; D013829:Thiadiazines / Q000494:pharmacology
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D008055:Lipids; D013829:Thiadiazines; C054860:NIP 200