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- W2088707972 abstract "Cyclosporin A (CsA) treatment has been reported to cause rises in serum bile acids both in humans and rats. It has also been shown to suppress bile flow in situ in rats and inhibit the transport of bile salts by rat hepatocytes. The purpose of this study was to examine the influence of CsA on uptake of radiolabelled cholate (CA), glycocholate (GC) and taurocholate (TC) by isolated human hepatocytes. CsA did not significantly change Vmax for CA uptake [0.23 ± 0.01 vs 0.25 ± 0.02 nmol/mg protein/min for control and CsA (10 μM), respectively], but significantly increased Km (37 ± 2 vs 86 ± 8 μM). Similarly, Vmax for TC uptake was not affected (0.51 ± 0.02 vs 0.67 ± 0.05 nmol/mg protein/min) while Km was significantly increased [46 ± 3 vs 109 ± 11 μM for control and CsA (10 μM), respectively). On the other hand, neither Vmax nor Km for GC uptake was affected by CsA. The data indicate a competitive pattern of inhibition induced by CsA on CA and TC uptake. Furthermore, CsA was found to cause a dose-related inhibition of accumulation of both cholate and taurocholate, but not GC accumulation. None of the concentrations of CsA showed a significant effect on the integrity of the human hepatocytes as assessed by ALT (alanine aminotransferase), AST (aspartate aminotransferase) and LDH (lactate dehydrogenase) release. The findings, in human hepatocytes, are generally consistent with the observations reported from rodent studies. They strongly support the contention that serum bile acid increases in CsA-treated patients are due to interference with the hepatocellular transport and accumulation of particular bile acids." @default.
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- W2088707972 date "1991-06-01" @default.
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- W2088707972 title "Substrate transport and cyclosporin A in isolated rat hepatocytes" @default.
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- W2088707972 doi "https://doi.org/10.1016/0006-2952(91)90701-6" @default.
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