Effect of NIP-200 on hyperlipidemia and atherosclerosis in cholesterol-fed rabbits.

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Abstract
The hypolipidemic and antiatherosclerotic effects of NIP-200 (3,5-dimethyl-4,6-diphenyl-tetrahydro-2H-1,3,5-thiadiazine-2-thione) 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 groups, 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 intenstine 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.