Arylsulfonate esters of fatty alcohols as hypocholesterolemic agents. I: Oleyl and linoleyl p‐toluenesulfonates

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Hypercholesterolemic rats, fed 1% cholesterol and 0.5% glycocholate, were treated with arylsulfonates in various ways to observe the pattern of cholesterol elimination. Dietary linoleyl p-toluenesulfonate (LTS) hastened return to normocholesterolemia and lowered hepatic cholesterol either with or without continued cholesterol feeding. LTS administered via the portal vein significantly lowered plasma cholesterol in 48 hr; ethyl linoleate and monoolein porduced no lowering. LTS administered via the portal vein to glycocholate-infused rats increased the biliary excretions of label from [4-14C] cholesterol administered intracardially and also increased total bile acid excretion 21% without increased bile volume when compared to similar injection of ethyl linoleate. No change in biliary excretion of cholesterol was seen. Bile acid kinetics were studied by using isotopic dilution techniques. Cholate turnover was enhanced by feeding oleyl p-toluenesulfonate (OTS) and oleyl p-(n-decyl)benzenesulfonate (ODS) as suggested by a 16-35% decrease in half-life in both normal and hypercholesterolemic rats. Rats consuming a grain-based colony diet had a 54% increase in cholate synthesis when OTS was included in the diet. The composition of bile was changed when either OTS or ODS was fed; an increase in chenodeoxycholate was noted. This change was gradual with OTS but rapid with ODS and paralleled enhanced decay of chenodeoxycholate specific radioactivity in response to treatment. ODS and OTS also increased 14CO 2 expiration from oral [26-14C] cholesterol in hypercholesterolemic rats. Dietary OTS andODS elevated hepatic free cholesterol in hypercholesterolemic rats; ODS also elevated plasma free cholesterol and increased cholesteryl ester hydrolase activity in the fiver. The data suggest that arylsulfonates stimulate cholesterol catabolism, in addition to the reported inhibition of cholesterol absorption [Lipids 12:819 (1977)].

Section: Introductionmentioning

confidence: 99%

Arylsulfonate esters of fatty alcohols: IV. Effects on cholesterol catabolism

Klauda

Bell

Grogan

et al. 1978

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Arylsulfonate esters as hypocholesteremic agents: III. Mechanism of action studies

MacNintch

Harris

Grogan

et al. 1977

The mechanism responsible for the hypocholestermic action of arylsulfonate esters of long chain fatty alcohols has been studied with rats fed either normocholesteremic or hypercholesteremic (1% cholesterol plus 0.5% glycoholate) diets. Linoleyl tosylate is more effective in lowering plasma and liver cholesterol levels of rats on the hypercholesteremic diet than several other hypocholesteremic agents tested. Linoleyl tosylate does not redistribute cholesterol to extrahepatic tissues nor inhibit hepatic cholesterol biosynthesis. Linoleyl tosylate is not effective in counteracting Triton-induced hypercholesteremia nor in lowering plasma cholesterol levels of the suckling rat. Linoleyl tosylate increases the fecal elimination of dietary [4(-14)C] cholesterol and prevents its accumulation in blood and liver. Oleyl p-(n-decyl) benzene sulfonate also prevents the apparent absorption of [26(-14)C] cholesterol from the gastrointestinal tract. Linoleyl tosylate increases the fecal excretion of neutral sterols but not of bile acids. The results indicate that the arylsulfonate esters of long chain fatty alcohols lower body cholesterol levels by inhibiting cholesterol absorption from the gastrointestinal tract. Exactly how absorption is inhibited is not clear, but linoleyl tosylate was found to stimulate the activity of cholesteryl esterase prepared from the intestinal mucosa.

The effect of arylsulfonate esters on cholesterol‐aggravated atherosclerosis in white carneau pigeons

MacNintch¹,

Clair

Lofland

et al. 1978

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The arylsulfonate esters of linoleyl, stearyl, and decyl alcohols were found to reduce significantly the accumulation of cholesterol in the plasma and livers of White Carneau pigeons subjected to a diet of Purina pigeon pellets coated with 0.25% cholesterol and 10% lard when fed for periods ranging from 9--12 months; no effects were observed in normocholesterolemic pigeons. These compounds produced no toxic side effects and were found to significantly attenuate the development of aortic atherosclerosis. The effect on aortic atherosclerosis was most likely the result of the lowering of plasma cholesterol concentrations. Linoleyl p-toluenesulfonate appeared to be the most effective of the three arylsulfonates tested, both with respect to the reduction of plasma and liver cholesterol accumulation and attenuation of the atherosclerotic process.