Fundamental studies on physiological and pharmacological actions of L-ascorbate 2-sulfate. I. On the hypolipidemic effects.

Abstract

SummaryThe effects of L-ascorbate 2-sulfate (AAS) on the lipid metabolism were examined in Triton-induced hyperlipemic mice, hyper cholesterolemic and normal rats, the following results being obtained. 1) In Triton-induced hyperlipemic mice, AAS (300mg/kg) significantly decreased the serum cholesterol level, while L-ascorbate (AA, 175mg/kg) was found ineffective.2) In hypercholesterolemic rats fed 0.5% cholester ol diet, the consecutive administration of AAS decreased the level of serum cholesterol and liver triacylglycerols. AA only slightly affected these levels. However, both AAS and AA prevented the unordinal increase in the liver weight caused by cholesterol feeding. 3) In normal rats, the administration of AAS over a 4-week period decreased the level of serum cholesterol and liver triacylglycerols.It is well known that sulfated polysaccharides have various pharmacological effects, such as being antipeptic (1) and anticoagulant (2) and having lipid lowering actions (3). In the course of the pharmacological study on sulfated monosac charides, we have found that L-ascorbate 2-sulfate (AAS) possesses an antipeptic (unpublished data) and cholesterol-lowering activity (4). The present paper deals with the effects of AAS on the lipid metabolism in the liver and serum from the Triton-treated mice, cholesterol-fed rats and normal rats. MATERIALS AND METHODSExperiment with Triton-induced hyperlipemic mice. Male mice of ddy strain, weighing 18-22 g, were divided into 7 groups of 10 animals each. Triton WR-1339 (800mg/kg, in saline) was intravenously administered into the tail vein to all animals, and simultaneously, AAS (300, 150, 75mg/kg), AA (300, 150mg/kg), 201

Fundamental Studies on Physiological and Pharmacological Actions of L-Ascorbate 2-Sulfate. Vi. Effects of L-Ascorbate 2-Sulfate on Lipid Metabolism in Guinea Pigs

“…Analyses of lipids and AA: Analysis of lipids in serum and liver were carried out as described in the previous papers (6,7). AA in various organs was extracted by homo genization with 1.4N acetic acid in 6 % metaphosphoric acid and centrifuging at 3,000 rpm for 15 min.…”

“…We reported in previous papers that AAS exerts lipid lowering effects in experimental hyperlipidemia with mice, rats and rabbits, and prevents development of atherosclerosis (6,7). In an attempt to dissociate the effect of AAS from that of L-ascorbic acid (AA), the present study of AAS on lipid metabolism has been carried out in guinea pigs which do not to biosynthesize AA in vivo.…”

Effect of L-ascorbate 2-sulfate on fatty liver and hyperlipidemia induced by various treatments in rats and guinea pigs.

“…It was reported that AAS has hypolipidemic effects in normal rats in a dose of 250mg/kg, in cholesterol-fed rats and rabbits in doses of 150 and 300mg/kg, and in cholesterol-fed guinea pigs at a dose of 300mg/kg, respectively (4)(5)(6). In this experiments, AAS was effective at a dose of 300 mg/kg on fatty liver and/or hyperlipidemia induced by various treatments (Tables 2 and 5).…”

“…Determinations of lipids in serum and liver and AA in various organs were carried out as described in previous papers (4,6). The results were statistically analyzed using Student's t-test.…”

The effect of vitamin C on the rapid induction of aortic changes in rabbits.

“…However, these levels were considerably altered over the 5-day injection period with a combination of cholesterol and ergocalciferol. While the significant hyper cholesterolemia (Table 3) was not as great as that observed after several months on a high-cholesterol diet, the increased triglycerides (Table 4) and decreased % HDL (Table 5) were of magnitudes consistent with the development of athero sclerosis (16). Increased % LDL, which occurs concomitant with decreased % HDL in rabbits (17) may be atherogenic by invasion of the endothelial wall (18).…”