scholarly journals Inhibition of .BETA.-sitosterol on intestinal cholesterol absorption in rat using in vivo dual isotope ratio method.

1980 ◽  
Vol 26 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Yoshihiro SHIDOJI ◽  
Makoto WATANABE ◽  
Tsuneyuki OKU ◽  
Yasutoshi MUTO ◽  
Norimasa HOSOYA
Keyword(s):  
Isotope Ratio ◽  
Cholesterol Absorption ◽  
Ratio Method ◽  
Intestinal Cholesterol Absorption ◽  
Dual Isotope

Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse

2003 ◽  
Vol 285 (3) ◽  
pp. G494-G502 ◽  
Author(s):  
David Q.-H. Wang ◽  
Susumu Tazuma ◽  
David E. Cohen ◽  
Martin C. Carey
Keyword(s):  
Bile Salt ◽  
Bile Acids ◽  
Cholesterol Absorption ◽  
Absorption Efficiency ◽  
Ratio Method ◽  
Susceptible Mouse ◽  
Hydrophobicity Index ◽  
Intestinal Cholesterol Absorption ◽  
Principal Mechanism ◽  
Dual Isotope

We explored the influence of the hydrophilic-hydrophobic balance of a series of natural bile acids on cholesterol absorption in the mouse. Male C57L/J mice were fed standard chow or chow supplemented with 0.5% cholic; chenodeoxycholic; deoxycholic; dehydrocholic; hyocholic; hyodeoxycholic; α-, β-, or ω-muricholic; ursocholic; or ursodeoxycholic acids for 7 days. Biliary bile salts were measured by reverse-phase HPLC, and hydrophobicity indices were estimated by Heuman's method. Cholesterol absorption efficiency was determined by a plasma dual-isotope ratio method. In mice fed chow, natural proportions of tauro-β-muricholate (42 ± 6%) and taurocholate (50 ± 7%) with a hydrophobicity index of -0.35 ± 0.04 produced cholesterol absorption of 37 ± 5%. Because bacterial and especially hepatic biotransformations of specific bile acids occurred, hydrophobicity indices of the resultant bile salt pools differed from fed bile acids. We observed a significant positive correlation between hydrophobicity indices of the bile salt pool and percent cholesterol absorption. The principal mechanism whereby hydrophilic bile acids inhibit cholesterol absorption appears to be diminution of intraluminal micellar cholesterol solubilization. Gene expression of intestinal sterol efflux transporters Abcg5 and Abcg8 was upregulated by feeding cholic acid but not by hydrophilic β-muricholic acid nor by hydrophobic deoxycholic acid. We conclude that the hydrophobicity of the bile salt pool predicts the effects of individual fed bile acids on intestinal cholesterol absorption. Natural α- and β-muricholic acids are the most powerful inhibitors of cholesterol absorption in mice and might act as potent cholesterol-lowering agents for prevention of cholesterol deposition diseases in humans.

scholarly journals Vitamin A Absorption Determined in Rats Using a Plasma Isotope Ratio Method

2020 ◽  
Vol 150 (7) ◽  
pp. 1977-1981 ◽  
Author(s):  
Michael H Green ◽  
Joanne Balmer Green
Keyword(s):  
Vitamin A ◽  
Oral Dose ◽  
Isotope Ratio ◽  
Cholesterol Absorption ◽  
Absorption Efficiency ◽  
Intravenous Dose ◽  
Ratio Method ◽  
Sprague Dawley ◽  
Retinyl Acetate ◽  
Dose Fraction

ABSTRACT Background Better methods are needed for determining vitamin A absorption efficiency. Objective Our objective was to measure vitamin A absorption in rats by adapting a plasma isotope ratio method previously used to determine cholesterol absorption. Methods Male Sprague-Dawley rats [n = 14; 340 ± 16 g (mean ± SD)] received an oral tracer dose of [3H]retinyl acetate in oil plus an intravenous dose of [14C]vitamin A–labeled lymph prepared in a donor rat that had received [14C]retinyl acetate intraduodenally. Blood samples were collected on days 1, 2, 3, 6, 9, and 12, and plasma was analyzed for 3H and 14C; vitamin A absorption was calculated for each sample as (fraction of oral dose/fraction of intravenous dose) × 100. Radioactivity was also measured in feces and urine collected as pools on days 3, 6, 9, and 12 and in liver and remaining carcass on day 12. Results Vitamin A absorption calculated as the plasma isotope ratio was >100% on day 1, 78% ± 5% on day 6, 76% ± 5% on day 9, and 74% ± 5% on day 12; fitting the data to an exponential function plus a constant predicted an absorption of 75% by day 14. Recovery of the oral dose in feces (day 0 to day 6) was low (6.2% ± 0.84%, n = 10) and the mean isotope ratio in day 9–12 urine pool was lower than that in plasma. Conclusions The plasma isotope ratio holds promise for estimating vitamin A absorption, but additional work is needed to determine how long studies need to be and if the doses should be administered simultaneously. For application of this method in humans, artificial chylomicrons labeled with a stable isotope of retinyl acetate could be used for the intravenous dose, with a different isotope required for the oral dose.

Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by affecting sphingomyelin levels in the gut: A study with NPP7 knockout mice

2014 ◽  
Vol 306 (10) ◽  
pp. G903-G908 ◽  
Author(s):  
Ping Zhang ◽  
Ying Chen ◽  
Yajun Cheng ◽  
Erik Hertervig ◽  
Lena Ohlsson ◽  
...  
Keyword(s):  
Cholesterol Absorption ◽  
Intestinal Content ◽  
Intestinal Lumen ◽  
Ratio Method ◽  
Physiological Factor ◽  
Dual Isotope ◽  
Alkaline Sphingomyelinase ◽  
Key Enzyme ◽  
In The Wild ◽  
Niemann Pick

We previously showed that dietary sphingomyelin (SM) inhibited cholesterol absorption in animals. The key enzyme hydrolyzing SM in the gut is alkaline sphingomyelinase (alk-SMase, nucleotide pyrophosphatase/phosphodiesterase 7). Here using the fecal dual-isotope ratio method we compared cholesterol absorption in the wild-type (WT) and alk-SMase knockout (KO) mice. The animals were fed an emulsion containing [14C]cholesterol and [3H]sitosterol. The radioactivities in the lipids of the fecal samples collected 4, 8, and 24 h thereafter were determined, and the ratio of 14C/3H was calculated. We found that the fecal [14C]cholesterol recovery in the KO mice was significantly higher than in the WT mice. A maximal 92% increase occurred 8 h after feeding. Recovery of [3H]sitosterol did not differ between the two groups. Accordingly, the 14C-to-3H ratio of fecal lipids was 133% higher at 8 h and 75% higher at 24 h in the KO than in the WT mice. Decreased [14C]cholesterol was also found in the serum of the KO mice 4 h after feeding. Supplement of SM in the emulsion reduced the differences in fecal [14C]cholesterol recovery between the WT and KO mice because of a greater increase of [14C]cholesterol recovery in the WT mice. Without treatment, the KO mice had significantly higher SM levels in the intestinal content and feces, but not in the intestinal mucosa or serum. The expression of Niemann-Pick C1 like 1 protein in the small intestine was not changed. In conclusion, alk-SMase is a physiological factor promoting cholesterol absorption by reducing SM levels in the intestinal lumen.

scholarly journals Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man.

1982 ◽  
Vol 23 (3) ◽  
pp. 480-489
Author(s):  
P Samuel ◽  
D J McNamara ◽  
E H Ahrens ◽  
J R Crouse ◽  
T Parker
Keyword(s):  
Isotope Ratio ◽  
Cholesterol Absorption ◽  
Ratio Method

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

Sign in / Sign up

Export Citation Format

Share Document