Effects of hincreased conversion ratio of tryptophan to niacin by the administration of clofibrate, a hypolipidemic drug, to rats

Abstract

The effect of clofibrate, a hypolipidemic drug and also known as a peroxisomal proliferator, on the conversion ratio of tryptophan to niacin was investigated by using rats. The rats were fed with a nicotinic acid-free, 20% casein diet (control group) or the same diet +0.25% clofibrate (clofibrate group) for 19 days. The conversion ratio gradually increased with increasing number of days. Around day 8, the ratio was about 10-times higher in the clofibrate group than in the control group, and the value remained almost constant after that day. The content of liver total nicotinamide was higher in the clofibrate group than in the control group. Among the enzymes involved in the conversion of tryptophan to niacin, the aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) activity, which is critical in the conversion, was lower in the clofibrate group than in the control group. As the change in ACMSDase activity took several days, there is a possibility that clofibrate decreased the biosynthesis of ACMSDase protein and/or mRNA. To learn whether the increase in the conversion ratio by clofibrate would be nutritionally meaningful or not, the growth-promoting activity of clofibrate was determined by using weanling rats fed with a nicotinic acid-free, tryptophan-limiting diet (basal diet). As a result, the body weight gain was higher in the clofibrate group than in the basal group. This result shows that clofibrate enhanced the conversion ratio without any side- effects under the conditions used and supports again the claim that the activity of ACMSDase exerts a critical influence on the tryptophan-NAD conversion. © 1996, Taylor & Francis Group, LLC. All rights reserved.