S-adenosyl-L-methionine reverses the cholestatic effect of ethinylestradiol in rat hepatocytes by increasing its catabolism

Larrauri, Amparo; Castell, José V.; Garrido, Guillermo; Berenguer, J; Gómez-Lechón, Marı́a José

doi:10.1007/bf00119292

Cited by 4 publications

References 26 publications

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S –Adenosyl–L–Methionine Prevents Disruption of Canalicular Function and Pericanalicular Cytoskeleton Integrity Caused by Cyclosporin A in Isolated Rat Hepatocyte Couplets

1996

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Isolated rat hepatocyte couplets were used to study the effect of S-adenosyl-L methionine (SAMe) treatment on disruption of canalicular function caused by cyclosporin A (CyA). Canalicular function was assessed by counting the percentage of couplets that were able to accumulate the fluorescent cholephile choly-lysyl-fluorescein (CLF) into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA). Cotreatment with 1 mmol/L SAMe prevented the inhibition of canalicular vacuole accumulation caused by CyA (75 nmol/L and 100 nmol/L), whereas treatment with it after CyA was unsuccessful. SAMe prevented the dose dependent reduction caused by CyA (5 nmol/L-1 mumol/L) both on CVA and on retention of CLF preaccumulated within the canaliculus, the effect on retention being complete. No difference in intracellular content of reduced glutathione (GSH) between the control and any dose level of the immunosuppressor, with or without SAMe treatment was observed, suggesting that changes in intracellular reduced GSH levels are not involved in the effects of SAMe. F-actin was stained with fluorescein-isothiocyanate phalloidin and fluorescence measurements were performed by confocal microscopy. The ratio of the percanalicular area fluorescence/total couplet fluorescence, indicative of F-actin distribution, significantly decreased with CyA. However, cotreatment of CyA with SAMe protected the integrity of the pericanalicular cytoskeleton, suggesting that this beneficial effect on canalicular function may maintain canalicular contractions and/or preserve tight junction function. Results are discussed in relation to possible involvement of the transmethylation pathway, modifications in membrane fluidity, effects on bile acid transport, and of inhibition of uptake of CyA. They suggest that SAMe could be a good candidate for protecting against CyA-induced membrane dysfunction.

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S –Adenosyl–L–Methionine Prevents Disruption of Canalicular Function and Pericanalicular Cytoskeleton Integrity Caused by Cyclosporin A in Isolated Rat Hepatocyte Couplets

1996

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[13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose oral contraceptives

1995

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The [13C]aminopyrine breath test measures hepatic mixed function oxidase activity. The cumulative percent dose recovered over 2 hr is a sensitive indicator of hepatic dysfunction; values < or = 7.0% have been shown to indicate severe liver disease. Previous studies have suggested that the test results may be influenced by the use of oral contraceptives steroids. We compared the results from five non-oral contraceptive-using women with those from 31 women whose duration of oral contraceptive steroid usage ranged from 4 to 204 months. The women were taking one of four oral contraceptive formulations that differed in the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5, 0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and 28 of the menstrual cycle. Cumulative percent dose recovery values among the normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/- 1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid users showed a marked reduction in cumulative percent dose recovery at 21 days, averaging 6.1 +/- 2.3% (P < 0.001), and returned to normal values (10.2 +/- 3.5%) at 28 days in most women(seven days after oral contraceptive steroid usage was paused). The adverse impact on hepatic mixed function oxidase by oral contraceptive formulations did not differ on the basis of estrogen or progesterone content. The adverse impact of oral contraceptive usage on the mixed function oxidase activity measured by the [13C]aminopyrine breath test must be considered for women of childbearing potential.

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Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

Petzinger¹

1994

Reviews of Physiology, Biochemistry and Pharmacology

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S-adenosyl-L-methionine reverses the cholestatic effect of ethinylestradiol in rat hepatocytes by increasing its catabolism

Cited by 4 publications

References 26 publications

S –Adenosyl–L–Methionine Prevents Disruption of Canalicular Function and Pericanalicular Cytoskeleton Integrity Caused by Cyclosporin A in Isolated Rat Hepatocyte Couplets

S –Adenosyl–L–Methionine Prevents Disruption of Canalicular Function and Pericanalicular Cytoskeleton Integrity Caused by Cyclosporin A in Isolated Rat Hepatocyte Couplets

[13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose oral contraceptives

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

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