Prevention of atherosclerotic lesion development in mice by taurine.
The antiatherosclerotic effects of taurine were evaluated in two murine models. In C57BL/6J mice fed a high-fat diet, 6-month treatment with taurine decreased serum atherogenic low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol by 44%. The same treatment increased antiatherogenic high-density lipoprotein (HDL) cholesterol by 25%. Hepatic cholesterol content was also decreased by taurine. Taurine improved the area of oil red O positive arterial lipid accumulation by 20%. Hepatic cholesterol 7 alpha-hydroxylase activity, a rate-limiting enzyme of bile acid synthesis from cholesterol, was doubled in taurine-treated mice, suggesting stimulation of cholesterol catabolism to bile acid as the cholesterol-lowering mechanism seen with taurine. Thus, taurine prevented the progression of atherosclerotic lesions, and concomitantly improved the serum lipoprotein profile. In another murine model, in apolipoprotein-E-deficient mice fed regular chow, a 3-month treatment with taurine prevented accumulation of arterial lipids by 31%, despite a significant increase in serum LDL and VLDL cholesterol levels. Serum thiobarbituric acid reactive substances (TBARS) in apolipoprotein-E-deficient mice were significantly higher than those in wild type mice and treatment with taurine lowered serum TBARS level by 26%. Thus, taurine prevents the development of atherosclerotic lesions and this antioxidative effect may play an important role in the antiatherosclerotic effect that is unrelated to serum cholesterol levels.
Murakami
S
S
Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Japan. s12867@ccm.taisho.co.jp
Kondo
Y
Y
Tomisawa
K
K
Nagate
T
T
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005487:Foam Cells / Q000187:drug effects / Q000473:pathology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013654:Taurine / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001057:Apolipoproteins E; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D013654:Taurine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase