Effects of Ethinyl Estradiol and Phenobarbital on Bile Acid Synthesis and Biliary Bile Acid and Cholesterol Excretion

Davis, Roger J.; Kern, Fred

doi:10.1016/s0016-5085(76)80325-3

Cited by 80 publications

(29 citation statements)

References 29 publications

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“…An elevated hepatic level of bile acids, as well as diminished bile flow, appear to be responsible for the reduction of Oct1 in the BDL model (43). However, EE cholestasis in the present study is characterized by the reduction of bile flow (Table I) and bile acid synthesis, with only a mild increase in bile acids in the serum, but not within hepatocytes (18,35,44), and minor morphological changes in hepatocytes with evidence of an increased mitotic index (17,34). Elucidation of the factors and mechanisms that regulate the expression of Oct1 in each cholestasis model will require further investigation.…”

Section: Intravenous Glucose Tolerance Testmentioning

confidence: 53%

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

et al. 2008

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Section: Intravenous Glucose Tolerance Testmentioning

confidence: 53%

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

et al. 2008

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“…This includes alterations in cholesterol homeostasis. Effects on cholesterol can be elicited through a number of mechanisms including: increased low-density lipoprotein uptake (Kovanen et al 1979), altered bile acid synthesis and secretion (Gumucio and Valdivieso 1971;Kreek et al 1969), esterification reactions (Davis and Kern 1976), or changes in de novo synthesis (Fewster et al 1967;Humber et al 1962;Mukherje and Bhose 1968;Wade et al 1984). In contrast to the extensive number of studies conducted to determine the effects of estrogens on cholesterol metabolism in mammals, only a handful of studies have investigated the effects of estrogens on cholesterol homeostasis in fish (Khanna and Singh 1983;Samuelsson et al 2006;Sharpe and MacLatchy 2007;Wallaert and Babin 1992).…”

Section: Effects Of Ee2 On Total Cholesterol In the Livermentioning

confidence: 99%

Profiling lipid metabolites yields unique information on sex- and time-dependent responses of fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol

et al. 2008

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Alterations in hepatic lipid profiles of fathead minnows (FHM) exposed to the synthetic estrogen 17a-ethynylestradiol (EE2) were determined using 1 H-NMR spectroscopy-based metabolite profiling. The exposures were conducted using either 10 ng/l or 100 ng/l EE2 via a continuous flow water delivery system. Livers were collected at 1, 4, and 8 days of the exposure and 8 days after the chemical was removed from the water (i.e. an 8 day depuration). The exposure resulted in a number of sex-specific changes in lipid profiles that were also highly time dependent. Those metabolites most affected by exposure included phosphatidylcholine, diglycerides, triglycerides and cholesterol. In addition, changes in the length and degree of unsaturation of hepatic fatty acids were observed. Lipid profiles in plasma for fish collected on the 4th day of exposure were also analyzed in order to provide further insights into changes observed in hepatic metabolite changes. Using validated partial least-squares discriminant analysis (PLS-DA), the response trajectories of the male liver lipid profiles at both exposure concentrations were compared. This analysis indicated that the males exposed to the low concentration of EE2 (10 ng/l) were largely able to recover from the exposure once the chemical was removed from the water. Conversely, the males exposed to the high concentration (100 ng/l) did not appear to recover from the exposure despite the 8 day depuration.

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“…In addition to impairing hepatocellular transport systems, EE inhibits BS synthesis; this reduces endogenous BS pool and, consequently, BS output [176,177]. The overall change in BS content is accompanied by a relative enrichment of the BS pool in both -muricholate ( -MC) and the secondary BS derived from its intestinal conversion, hyodeoxycholate (HDC).…”

Section: Estrogen-induced Cholestasismentioning

confidence: 99%

“…A key mechanism by which EE impairs BS output is inhibition of the overall BS synthetic pathway [176,177], a finding mainly attributed to the inhibitory effect of EE on Cyp7a1. SIL completely prevented the decrease induced by EE in the size of the endogenous BS pool produced by the inhibition of BS synthesis; this explains the improvement in BS output induced by SIL.…”

Section: Prevention Of Estrogen-induced Cholestasis By Silmentioning

confidence: 99%

Silymarin as a New Hepatoprotective Agent in Experimental Cholestasis: New Possibilities for an Ancient Medication

Crocenzi¹,

Roma²

2006

CMC

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Silymarin is a purified extract from milk thistle (Silybum marianun (L.) Gaertn), composed of a mixture of four isomeric flavonolignans: silibinin (its main, active component), isosilibinin, silydianin and silychristin. This extract has been empirically used as a remedy for almost 2000 years, and remains being used as a medicine for many types of acute and chronic liver diseases. Despite its routinely clinical use as hepatoprotectant, the mechanisms underlying its beneficial effects remain largely unknown. This review addresses in detail a number of recent studies showing a novel feature of silymarin as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. For this purpose, this review will cover the following aspects: 1. The chemistry of silymarin, including chemical composition and properties. 2. The current clinical applications of silymarin as a hepatoprotective agent, including the mechanisms by which silymarin is thought to exert its hepatoprotective properties, when known. 3. The physiological events involved in bile formation, and the mechanisms of hepatocellular cholestasis, focusing on cellular targets and mechanisms of action of drugs used to reproduce experimentally cholestatic diseases of clinical interest, in particular estrogens and monohydroxylated bile salts, where anticholestatic properties of silymarin have been tested so far. 4. The recent findings describing the impact of silymarin on normal bile secretion and its novel, anticholestatic properties in experimental models of cholestasis, with particular emphasis on the cellular/molecular mechanisms involved, including modulation of bile salt synthesis, biotransformation/depuration of cholestatic compounds, changes in transporter expression/activity, and evocation of signaling pathways.

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Effects of Ethinyl Estradiol and Phenobarbital on Bile Acid Synthesis and Biliary Bile Acid and Cholesterol Excretion

Cited by 80 publications

References 29 publications

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

Reduced Antidiabetic Effect of Metformin and Down-regulation of Hepatic Oct1 in Rats with Ethynylestradiol-Induced Cholestasis

Profiling lipid metabolites yields unique information on sex- and time-dependent responses of fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol

Silymarin as a New Hepatoprotective Agent in Experimental Cholestasis: New Possibilities for an Ancient Medication

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