Effect of 3,4-di(OH)-cinnamate synthetic derivative on plasma and hepatic cholesterol level and antioxidant enzyme activities in high cholesterol-fed rats

• Published in: Journal of biochemical and molecular toxicology 2004-01, Vol.18 (5), p.279-287
• Main Authors: Park, Eun-Jin, Lee, Sangku, Jeong, Tae-Sook, Bok, Song-Hae, Lee, Mi-Kyung, Park, Yong Bok, Choi, Myung-Sook
• Format: Article
• Language: English
• Subjects: 3,4‐Di(OH)‐phenylpropionic L‐Phenylalanine amide; 4-Di(OH)-phenylpropionic L-Phenylalanine amide; Animals; Antioxidant Enzymes; Caffeic Acids - pharmacology; Cholesterol - blood; Cholesterol, Dietary; Coumaric Acids - pharmacology; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Hydroxymethylglutaryl CoA Reductases - metabolism; Lipid Profiles; Liver - drug effects; Liver - metabolism; Lovastatin - pharmacology; Male; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacology; Rats; Rats, Sprague-Dawley; Sterol O-Acyltransferase - metabolism; Superoxide Dismutase - metabolism
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.20036

The effect of 3,4‐di(OH)‐phenylpropionic acid (L‐phenylalanine methyl ester) amide (SL‐1063), a synthetic derivative of 3,4‐di(OH)‐cinnamate, on the cholesterol metabolism and antioxidant enzyme system was examined in rats. Diets that included either SL‐1063 (0.046%, w/w) or lovastatin (0.02%, w/w) as a supplement, plus 1 g cholesterol/100 g diet were fed to rats ad libitum for 5 weeks. The total plasma cholesterol and triglyceride levels were significantly lowered by the SL‐1063 supplement compared to the control group. Meanwhile, the levels of plasma HDL‐cholesterol and ratio of HDL‐cholesterol/total cholesterol (%) were significantly higher in the SL‐1063 group than in the control group. However, the lovastatin supplement did not affect the plasma lipid level. The hepatic cholesterol level and 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase activity were significantly lowered in the lovastatin group compared to the SL‐1063 group; however, the hepatic triglyceride level did not differ among the groups. The activity of hepatic acyl CoA: cholesterol acyltransferase (ACAT), the enzyme that catalyzes hepatic cholesterol esterification, was significantly lower in the lovastatin and SL‐1063 groups than in the control group. Furthermore, the SL‐1063 supplement elevated the excretion of fecal sterols. As regards the hepatic antioxidant enzyme system, the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px), and glutathione reductase (GR) activities were all significantly higher in the SL‐1063 group compared to the control group, whereas only the GR activity was significantly increased by the lovastatin supplement. No marked difference in the GSH levels and glucose‐6‐phosphate dehydrogenase (G6PD) activities was observed among the groups. The levels of plasma and hepatic thiobarbituric acid reactive substances (TBARS) were lowered by the SL‐1063 supplement compared to the control group. Accordingly, the current results suggest that SL‐1063, a synthetic derivative of 3,4‐di(OH)‐cinnamate, is effective in lowering the plasma lipids and improving the antioxidant enzyme system. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:279–287, 2004 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20036