Effect of Simvastatin, Ursodeoxycholic Acid and Simvastatin Plus Ursodeoxycholic Acid on Biliary Lipid Secretion and Cholic Acid Kinetics in Nonfamilial Hypercholesterolemia

Mazzella, Giuseppe; Parini, Paolo; Festi, Davide; Bazzoli, Franco; Aldini, Rita; Roda, Aldo; Tonelli, Domenica; Cipolla, Antonio; Salzetta, Antonio; Roda, Enrico

doi:10.1002/hep.1840150617

Cited by 42 publications

(38 citation statements)

References 44 publications

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“…Patients volunteered for the lithogenicity of bile. [4][5][6][7] It has been suggested that the reduc-study, which had been approved by the ethics committee of our hospition of biliary cholesterol secretion is caused by increased tal. conversion of cholesterol to bile acids 8 and malabsorption of Lipid Analysis.…”

Section: Methylase Steps Resulting In Decreased Biliary Secretionmentioning

confidence: 99%

The Effects of Ursodeoxycholic Acid on Serum and Biliary Noncholesterol Sterols in Patients With Gallstones

1997

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increase in cholesterol synthesis to maintain the body pool Litholytic bile acid ursodeoxycholic acid (UDCA) reof cholesterol unless the decrease in biliary cholesterol secreduces biliary cholesterol secretion and alters cholesterol tion is sufficient to compensate for reduced cholesterol abmetabolism by mechanisms that are not fully undersorption. However, the effect of UDCA on cholesterol metabostood. To evaluate cholesterol metabolism during UDCA lism, especially on cholesterol synthesis, has not been treatment, we studied serum and biliary lipids and choevaluated thoroughly, and the results available are controlesterol precursor sterols (lanosterol and other dimethyl versial, varying from suppression to no effect. 11,13-15 and monomethyl sterols, lathosterols, and desmosterol), Human serum and bile contains, in addition to cholesterol, indicators of cholesterol synthesis, and plant sterols small amounts of noncholesterol sterols, including cholesterol campesterol and sitosterol, indicators of cholesterol abprecursor 16 and dietary plant sterols. 17 Normally and in many sorption, before and during administration of UDCA, 9clinical conditions, the ratios of serum cholesterol precursor mg/kg/d, for 26 weeks in eight patients with radiolucent sterols to cholesterol have been shown to be correlated with gallstones. During UDCA administration, serum lipid the rate of cholesterol synthesis, 16,[18][19][20][21] whereas the serum concentrations were unchanged, but the biliary concenplant sterol levels indicate cholesterol absorption efficiency. 22 tration and molar percentage of cholesterol were markAccordingly, the serum and biliary noncholesterol sterol levedly decreased. The proportions of the cholesterol els might give some additional information on possible precursor sterols to cholesterol were significantly interchanges in cholesterol absorption and synthesis during related between serum and bile before and especially UDCA treatment. To this end we studied the serum and biliduring UDCA administration. Lanosterol and lathosary cholesterol precursor and plant sterol levels in gallstone terol levels, especially in bile, were significantly depatients before and during UDCA treatment to evaluate the creased by 43% and 34%, suggesting that UDCA may ineffects of this treatment on cholesterol absorption and metabhibit cholesterol synthesis. Levels of the other olism. methylase steps, resulting in decreased biliary secretionAfter the baseline studies they started UDCA, 9 mg/kg/d in two daily of cholesterol. Reduced biliary sterol secretion probably doses. Two patients used UDCA for only 4 weeks, whereas the other increased serum plant sterol levels, indicating that un-six patients used it for 6 months. However, 4 weeks' treatment was der these conditions they no longer reflect the intestinal enough to reach metabolic steady-state because in the six long-term efficiency of cholesterol absorption. (HEPATOLOGY patients the biliary molar percentages of cholesterol were similar 1997;25:514-518.) when analyzed after 4 weeks ...

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Section: Methylase Steps Resulting In Decreased Biliary Secretionmentioning

confidence: 99%

The Effects of Ursodeoxycholic Acid on Serum and Biliary Noncholesterol Sterols in Patients With Gallstones

1997

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“…UDCA, as an endogenous tertiary bile acid in man, has several biologic effects, such as inhibition of cholesterol absorption in the intestine [36] and inhibition of bile secretion [37] , stabilization of cell membrane [38] and modulation of immunologic reactions [39] . Recent reports suggested that the novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells [8] .…”

Section: Discussionmentioning

confidence: 99%

Mechanism of apoptotic effects induced selectively by ursodeoxycholic acid on human hepatoma cell lines

Liu¹

2007

WJG

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AIM:To investigate the effects of ursodeoxycholic acid (UDCA) on apoptosis and proliferation of hepatoma cell lines. METHODS:Human hepatoma cell lines HepG2 and BEL 7402 were cultured in medium supplemented with different concentrations of UDCA, normal human hepatic line L-02 was used as control. Cell proliferation, apoptosis and gene expression were detected using methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, Western blot, DNA ladder assay, electron microscopy, and immunocytochemistry. RESULTS:Ursodeoxycholic acid inhibited the proliferation of HepG2 and BEL7402 cell lines in a dosedependent manner. Ursodeoxycholic acid can change cell cycle distribution of HepG2 and BEL7402, the proportion of cells in G0-G1 phase increased whereas the proportion of S phase cells and G2-M phase cells decreased. Ursodeoxycholic acid arrested the cell cycle in G0-G1 phase by down-regulating the cell cycle related proteins cyclin D1, D3 and retinoblastoma protein (p Rb ). The apoptotic rates of HepG2 and BEL7402 treated with UDCA (1.0 mmol/L) were significantly higher than those of control. In the HepG2 and BEL7402 treated with UDCA, expression of bcl-2 decreased whereas expression of Bax increased, the nuclear fragmentation and chromosomal condensed, cells shrank and lost attachment, apoptotic bodies and DNA ladders appeared. UDCA had no effect in inducing apoptosis on L-02 cell lines. CONCLUSION:UDCA can selectively inhibit proliferation and induce apoptosis of HepG2 and BEL7402 cell lines by blocking cell cycle and regulating the expression of Bax/bcl-2 genes.

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“…It also reduces the cholesterol content of bile relative to bile acid and lecithin, a change that might theoretically be conducive to prevention or dissolution of cholesterol gallstones (2,3). Two related drugs, simvastatin and pravastatin, appear to have similar effects (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects.

Duane¹

1993

J. Clin. Invest.

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We measured biliary and fecal sterol outputs in 12 human subjects on a metabolic ward in four randomly allocated, [6][7] Judging from these data, the primary action of lovastatin is to lower cholesterol synthesis and systemic cholesterol input, the main compensatory response being reduced biliary cholesterol secretion. Conversely, increased dietary cholesterol appears to increase systemic cholesterol input, the major compensatory response being increased bile acid synthesis. There appears to be no interaction between these two perturbations of systemic cholesterol input. (J. Clin. Invest. 1993. 92:911-918.)

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Effect of Simvastatin, Ursodeoxycholic Acid and Simvastatin Plus Ursodeoxycholic Acid on Biliary Lipid Secretion and Cholic Acid Kinetics in Nonfamilial Hypercholesterolemia

Cited by 42 publications

References 44 publications

The Effects of Ursodeoxycholic Acid on Serum and Biliary Noncholesterol Sterols in Patients With Gallstones

The Effects of Ursodeoxycholic Acid on Serum and Biliary Noncholesterol Sterols in Patients With Gallstones

Mechanism of apoptotic effects induced selectively by ursodeoxycholic acid on human hepatoma cell lines

Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects.

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