Studies on Hypolipidemic Agents. V. : Influence of 5-Tridecylpyrazole-3-carboxylic Acid, a New Hypolipidemic Agent, on Intestinal Cholesterol Absorption in Rats

In order to clarify the inhibitory mechanism of 5-tridecylpyrazole-3-carboxylic acid (TDPC) on the absorptive process of cholesterol, the effects of this agent on micelle in vitro and intestinal uptake of cholesterol in rats as measured by the ligated-loop method in situ were investigated using β-sitosterol as a reference agent.TDPC did not affect the micellar formation of distribution of micellar size, both of which are important determinants in the process of cholesterol uptake, but β-sitosterol increased the distribution of large-size micelles (>450nm).TDPC significantly decreased the intestinal cholesterol uptake by 27%, 44% and 59% at the dose levels of 0.25, 0.50 and 1.0mg, respectively. Similarly, β-sitosterol significantly decreased the cholesterol uptake by 79% at the dose of 1.0mg.It is apparent from the above data that the hypocholesterolemic activity of TDPC and β-sitosterol partly depends on interference with intestinal cholesterol uptake, though there is a difference between the two agents in terms of the effect on micellar size. It can be assumed that both energy-dependent and -independent systems are involved in the process of the intestinal cholesterol uptake, and hte inhibitory effect of TDPC might berelated to the energy-independent system rather than the energy-dependent system.