Cyclosporin a increases the thight junctional permeability in rat liver

Lora, L.; Martines, Diego; Plebani, Mario; Floreani, Annarosa; Salvagnini, M.; Naccarato, R.

doi:10.1016/0168-8278(91)91170-l

Cited by 2 publications

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“…We analyzed the effect on cVR of CLF of a variety of toxicants which were shown to affect biliary permeability in intact liver by different mechanisms. They comprise the cholestatic agents CyA (Lora et al, 1991), 17/J-EG (Kan et al, 1989), and TLC (Boyer et al, 1976;Vu et al, 1992), as well as the calcium ionophore A23187 (Kan and Coleman, 1988) and the oxidative stress inducers menadione (Kan and Coleman, 1990) and f-BuHP (Ballatori and Truong, 1989). These compounds all decreased cVR of CLF in a dose-dependent manner and at concentrations at or below those that had been instrumental in impairing biliary permeability in the studies quoted above.…”

Section: Vpmentioning

confidence: 99%

“…An alternative quantitative approach was introduced by Nathanson et al (1992), who recorded changes in paracellular permeability induced by hormonal messengers, by assessing the percentage of couplets which were penetrated by exogenously administered HRP. In preliminary studies from our laboratory (Stone et al, 1994;Roman and Coleman, 1994) we observed that canalicular retention of the preaccumulated, fluorescent, conjugated bile acid analogue cholyl-lysyl-fluorescein (CLF) was impaired by 2-methyl-1,4-naphthoquinone (menadione) and cyclosporin A (CyA), two compounds known to affect biliary permeability in intact liver (Kan and Coleman, 1990;Lora et al, 1991). Since canalicular retention of cholephilic compounds requires tight junctions to be sealed (Wilton et al, 1993b), these observations raise the interesting possibility that changes in canalicular retention of CLF may actually reflect modifications of paracellular permeability in couplets.…”

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Canalicular Retention as an in Vitro Assay of Tight Junctional Permeability in Isolated Hepatocyte Couplets: Effects of Protein Kinase Modulation and Cholestatic Agents

1997

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A simple, fast method to evaluate acute changes of tight junctional permeability in isolated hepatocyte couplets is proposed. The method consists of the recording of the number of canalicular vacuoles able to retain the previously accumulated fluorescent bile acid analogue cholyl-lysyl-fluorescein (CLF), as visualized by inverted fluorescent microscopy, following acute exposure to the compounds under study. The method was validated by (i) making a systematic documentation of the effect on CLF retention of a variety of hormonal modulators (vasopressin and phorbol esters), as well as several cholestatic (taurolithocholic acid, cyclosporin A, and estradiol 17/3-glucuronide) and hepatotoxic agents (menadione, A23187, and t-butyl hydroperoxide), all known to affect biliary permeability in intact liver, and (ii) carrying out a comparative analysis of the results obtained with those recorded using rapid canalicular access of horseradish peroxidase (HRP) as an alternative procedure. The compounds tested all decreased canalicular vacuolar retention of CLF in a dose-dependent manner. Vasopressin-and phorbol ester-induced decline in CLF retention were prevented by pretreatment with the protein kinase C inhibitors H-7 and staurosporine, thus confirming a role for this enzyme in canalicular permeability regulation. A significant direct correlation (r = 0.934, p < 0.001) was obtained when the decrease in canalicular retention of CLF was compared with the increment in the canalicular access of HRP. Image analysis revealed that cellular fluorescence was not increased following exposure to these compounds, suggesting a paracellular rather than transcellular route for CLF egress. These results all support canalicular vacuolar retention of CLF as a suitable method to readily evaluate acute changes in tight junctional permeability in isolated hepatocyte couplets induced by physiological modulators or hepatotoxic agents, c IW? soday or To

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confidence: 99%

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confidence: 99%

Canalicular Retention as an in Vitro Assay of Tight Junctional Permeability in Isolated Hepatocyte Couplets: Effects of Protein Kinase Modulation and Cholestatic Agents

1997

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Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man

Erlinger

Desruenne

et al. 1992

Digest Dis Sci

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Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.

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Cyclosporin a increases the thight junctional permeability in rat liver

Cited by 2 publications

References 0 publications

Canalicular Retention as an in Vitro Assay of Tight Junctional Permeability in Isolated Hepatocyte Couplets: Effects of Protein Kinase Modulation and Cholestatic Agents

Canalicular Retention as an in Vitro Assay of Tight Junctional Permeability in Isolated Hepatocyte Couplets: Effects of Protein Kinase Modulation and Cholestatic Agents

Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man

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