Future therapeutic targets for the treatment and prevention of cholesterol gallstones

Castro-Torres, Ibrahim Guillermo; Cárdenas-Vázquez, R; Velázquez, Claudia; Ventura-Martı́nez, Rosa; O-Arciniega, Minarda De la; Naranjo‐Rodríguez, Elia Brosla; Martínez‐Vázquez, Mariano

doi:10.1016/j.ejphar.2015.08.045

Cited by 17 publications

(13 citation statements)

References 54 publications

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“…Our findings in this hamster model suggest that induction of hepatic SR-BI expression may account for the hypocholesterolemic effect of OCA under hyperlipidemic states. involved in phospholipid secretion (45) and is shown not to be dependent on biliary sterol secretion (46), a model emerges in hyperlipidemic hamsters in which the increased hepatic uptake of cholesterol esters from HDL via SR-BI and enhanced HDL metabolism by EL, coupled with increased cholesterol excretion via ABCB4 lead to stimulated transhepatic cholesterol efflux in hyperlipidemic hamsters by OCA treatment. Further investigations using radioisotope-labeled cholesterol to demonstrate a direct effect of OCA on upregulation of HDL-C uptake in SR-BI wild-type and deficient animals will be required to validate this working model.…”

Section: Lxr Activation Alone Did Not Induce Hepatic Expression Of Srmentioning

confidence: 99%

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters

Dong

Young

Liu

et al. 2017

Journal of Lipid Research

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Section: Lxr Activation Alone Did Not Induce Hepatic Expression Of Srmentioning

confidence: 99%

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters

Dong

Young

Liu

et al. 2017

Journal of Lipid Research

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“…Alterations in cholesterol transport across the canalicular membrane of hepatocytes have been suggested to be involved with gallstone formation. The modulation of ABCG5/8 activity might be used to control cholesterol and prevent gallstone formation [14] . An animal study using C57BL/6 mice, reported that piperine, a potential cholesterol lowering agent, inhibited ABCG5/8 and reduced cholesterol transport from the hepatocytes to the gallbladder [15] .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone

Kim

et al. 2017

Dig Dis

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Background: The increased risk of gallstone has been reported in patients with ATP-binding cassette (ABC) transporter polymorphism. The half-transporters ABCG5 and ABCG8 mediate the efflux of cholesterol in hepatocytes and the intestine. We investigated whether ceramide plays a role in cholesterol efflux through the ABC transporters. Methods: Six-week-old C57BL/6J mice were assigned to 3 groups. The normal group (n = 5) was fed a normal chow diet, the cholesterol group (n = 10) was fed a lithogenic diet, and the myriocin group (n = 15) was fed the lithogenic diet and myriocin, a specific inhibitor of serine-palmitoyl transferase. After 6 weeks, the ABCG5 and ABCG8 transporters were analyzed. Results: The rate of cholesterol gallstone formation in cholesterol group was also higher than that in normal and myriocin groups (0, 70, and 40%, respectively). ABCG5 and ABCG8 mRNA levels were significantly increased in cholesterol group and less increased in myriocin group, relative to that in normal group (p < 0.05). Conclusions: The inhibition of ceramide biosynthesis by myriocin suppressed gallstone formation and ABCG5/8 mRNA expression. We expect that ceramide's role as a regulator of the ABCG5/8 transporter might be linked to cholesterol gallstone formation.

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“…Neither of the rats fed hypercholesterolemic diets was treated with the extract [ 13 ]. On the other hand, it is known that Abcg5 and Abcg8 proteins are responsible for mediating cholesterol efflux [ 14 ]. Therefore, inhibition of these proteins could trigger a hypercholesterolemia process [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Hypocholesterolemic Effects of Eryngium carlinae F. Delaroche Are Mediated by the Involvement of the Intestinal Transporters ABCG5 and ABCG8

Castro-Torres

O-Arciniega

Naranjo‐Rodríguez

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Hypercholesterolemia is a metabolic disorder characterized by a high concentration of cholesterol in the blood. Eryngium carlinae is a medicinal plant used to treat lipid diseases. The goal of this work was to evaluate, in a model of hypercholesterolemia in mice, the hypocholesterolemic effect of a hydroalcoholic extract of E. carlinae and its main metabolite, D-mannitol. Biochemical analyses of serum lipids and hepatic enzymes were performed by photocolorimetry. We performed histopathological studies of the liver and the expression of the intestinal cholesterol transporters Abcg5 and Abcg8 was determined by standard western blot method. Our results showed that hydroalcoholic extract at doses of 100 mg/kg and D-mannitol at doses of 10 mg/kg reduced the concentration of both total cholesterol and non-HDL cholesterol, without altering the concentration of HDL cholesterol and without damage to hepatocytes. Treatment with the extract increased Abcg8 intestinal transporter expression, while D-mannitol decreased the expression of the two Abcg5/Abcg8 transporters, compared with the hypercholesterolemic group. Considering that Abcg5/Abcg8 transporters perform cholesterol efflux, our results demonstrate that the lipid-lowering effect of the hydroalcoholic extract may be associated with the increase of Abcg8 expression, but the hypocholesterolemic effect of D-mannitol is independent of overexpression of these intestinal transporters and probably they have another mechanism of action.

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Future therapeutic targets for the treatment and prevention of cholesterol gallstones

Cited by 17 publications

References 54 publications

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters

Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone

The Hypocholesterolemic Effects of Eryngium carlinae F. Delaroche Are Mediated by the Involvement of the Intestinal Transporters ABCG5 and ABCG8

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