Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro study in perifused rat hepatocytes

Pazzi, P.; Puviani, A.C.; Libera, Mauro Dalla; Guerra, Giovanni; Ricci, Daniele; Gullini, S.; Ottolenghi, C

doi:10.1097/00042737-199707000-00011

Cited by 26 publications

(22 citation statements)

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“…A report by Pazzi et al (1997), however, indicates that addition of UDCA significantly reduced the hepatotoxic effect of the lipophilic bile acid, deoxycholate but not chenodeoxycholate. These studies were made with freshly isolated rat hepatocytes suspended on a resin column and perfused with different concentrations of bile acids (Pazzi et al, 1997). Galle et al (1990) also reported a decrease of toxicity of GCDC by UDCA in primary human hepatocytes.…”

Section: Resultsmentioning

confidence: 95%

Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism

2002

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Cholestasis results from hepatocyte dysfunction due to the accumulation of bile acids in the cell, many of which are known to be cytotoxic. Recent evidence implicates competitive antagonism of key cytotoxic responses as the mechanism by which certain therapeutic bile acids might afford cytoprotection against cholestasis. In this work, we compare the relative cytotoxicity of bile acids in terms of dose-and time-dependence. To better elucidate the controversy related to the therapeutic use of ursodeoxycholate (UDCA) in cholestatic patients, we also evaluated the effects of bile acid combinations. Viability of Wistar rat hepatocytes in primary culture was measured by LDH leakage after 12 and 24 h exposure of cells to the various bile acids. All unconjugated bile acids caused a dose-dependent decrease in cell viability. The tauro-and glyco-conjugates of chenodeoxycholate (CDCA) and UDCA were all less toxic than the corresponding unconjugated form. Although relatively non-toxic, UDCA caused synergistic cell killing by lithocholate (LCA), CDCA, glyco-CDCA (GCDC) and tauro-CDCA (TCDC). Glycoursodeoxycholate decreased the toxicity of GCDC, but potentiated the toxicity of unconjugated CDCA and LCA. The tauro-conjugate of UDCA had no significant effect. These data suggest that at cholestatic concentrations, bile acid-induced cell death correlates with the degree of lipophilicity of individual bile acids. However, these results indicate that the reported improvement of biochemical parameters in cholestatic patients treated with UDCA is not due to a direct effect of UDCA on hepatocyte viability. Therefore, any therapeutic effect of UDCA must be secondary to some other process, such as altered membrane transport or nonparenchymal cell function.

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Section: Resultsmentioning

confidence: 95%

Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism

2002

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“…With the redesigned assay, p,p´-DDT exhibited moderate estrogenic activity, in contrast with the RS assay (16) where p,p´-DDT gave no response. The 95% confidence intervals for EC 50 values and efficiency of the test compounds are summarized in Table 1. Incubation of the recombinant yeast with bisphenol A resulted in a 100% efficiency, while the highest concentrations of methoxychlor, p,p´-DDT, and genistein reached an efficiency of 77, 11, and 65%, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Bile salts occur in the intestine in a concentration ranging from 0.1 to 5 mmol/L, and they play an important role in solubilization of dietary lipids. However, bile salts in this concentration range also disrupt membrane integrity and are toxic to bacteria, isolated hepatocytes, and colonic mucosa (48)(49)(50)(51). The extracts obtained from samples of digested soygerm powder incubated with a microbial suspension exhibited a significantly higher (p ≤ 0.05) absorbance at 575 nm compared to the control with ethanol, which points to estrogenic activity.…”

Section: Discussionmentioning

confidence: 99%

“…The data were fitted by a 4 parametric logistic model using the MarquardtLevenberg algorithm (Sigmaplot 4.0, SPSS Inc., Chicago, Illinois, USA). Efficiency (maximal response) and potency values (median effective concentration; EC 50 ) were obtained by the parameters of the fitted function.…”

Section: Methodsmentioning

confidence: 99%

“…Parameter EC 50 gives the transition center and equals the potency, which is the concentration that causes 50% efficiency. The hillslope determines the slope of the curve at the transition center.…”

Section: Methodsmentioning

confidence: 99%

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Optimization of a yeast estrogen screen and its applicability to study the release of estrogenic isoflavones from a soygerm powder.

Boever

Demaré

Vanderperren

et al. 2001

Environ Health Perspect

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Here we describe a redesigned protocol of the yeast estrogen screen developed by Routledge and Sumpter. The redesigned test comprises two steps. First, a large amount of yeast with estrogenic compounds is incubated for 24 hr. Subsequently, a mixture of cycloheximide and the chromogenic substrate chlorophenol red-beta-d-galactopyranoside (CPRG) is added. The cycloheximide stops protein synthesis and allows for an end-point measurement of beta-galactosidase activity generated during the first 24 hr. CPRG is converted to chlorophenol red and reflects beta-galactosidase activity, which is indicative of the estrogenic activity. The modifications shorten the duration of the assay at least 1 day and avoid interference of the estrogenic CPRG or chlorophenol red. The redesigned and the original protocol were used to study the estrogenic activity of bisphenol A, methoxychlor, p,p'-DDT, and isoflavones (genistein, daidzein, and glycitein). Bisphenol A, methoxychlor, and genistein triggered higher levels of beta-galactosidase activity in the redesigned protocol. Estrogenic activity of p,p'-DDT could only be demonstrated with the redesigned protocol. Glycitein and daidzein failed to give a response with both protocols. We also studied deconjugation of beta-glycosidic isoflavones present in soygerm powder. Treatment of the soygerm powder with beta-glycosidase released isoflavones. The estrogenic response of the samples was confirmed with the redesigned protocol and correlated with the amount of genistein present. The release of isoflavones under conditions prevailing in the intestines was studied. Bacterial beta-glycosidase present in the large intestine released isoflavones, and moderate estrogenic activity could be demonstrated.

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Probiotic Bile Salt Hydrolase: Current Developments and Perspectives

Patel

Singhania

Pandey

et al. 2009

Appl Biochem Biotechnol

129

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Probiotic has modernized the current dietetic sense with novel therapeutic and nutritional benefits to the consumers. The presence of bile salt hydrolase (BSH) in probiotics renders them more tolerant to bile salts, which also helps to reduce the blood cholesterol level of the host. This review focuses on the occurrence of bile salt hydrolase among probiotics and its characterization, importance, applications, and genetics involved with recent updates. Research on bile salt hydrolase is still in its infancy. The current perspective reveals a huge market potential of probiotics with bile salt hydrolase. Intensive research in this field is desired to resolve some of the lacunae.

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Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro study in perifused rat hepatocytes

Cited by 26 publications

References 0 publications

Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism

Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism

Optimization of a yeast estrogen screen and its applicability to study the release of estrogenic isoflavones from a soygerm powder.

Probiotic Bile Salt Hydrolase: Current Developments and Perspectives

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