Mechanisms of the hypolipidemic effect of NIP-200 in rats.
We studied the mechanisms of hypolipidemic effects of NIP-200 (3,5-dimethyl-4,6-diphenyltetrahydro-2H-1,3,5-thiadiazine- 2-thione), a potent hypolipidemic compound, in cholesterol biosynthesis in the liver, cholesterol absorption in small intestine, and cholesterol catabolism and excretion in rats. NIP-200 did not reduce cholesterol biosynthesis and had no effects on cholesterol absorption in the small intestine. In the cholesterol catabolism and excretion, NIP-200 induced increases in cholesterol and bile acids levels in the bile and acidic steroids in the feces, and it enhanced cholesterol 7 alpha-hydroxylase activity in the liver. These results suggest that NIP-200 increases the synthesis of bile acids as a result of the activation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the conversion of cholesterol to bile acids. Therefore, it is considered that one of the probable mechanisms of the serum total cholesterol lowering action of NIP-200 involves the enhancement of catabolism and excretion of cholesterol in the liver.
Sakashita
M
M
Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
Toyoda
K
K
Kitahara
M
M
Tsuruzoe
N
N
Nakayama
S
S
Oguchi
K
K
D000818:Animals; D001646:Bile / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D006949:Hyperlipidemias / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013829:Thiadiazines / Q000494:pharmacology*
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D013829:Thiadiazines; C054860:NIP 200; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase