Purpose: The possible mechanisms of increased thiol me-thyltransferase (TMT) activity in cholestatic rat livers and serum were studied.
Methods: Rats were divided into seven groups: rats receiving a sham operation, rats with a bile duct obstruction (BDO) alone (BDO group), rats with BDO plus taurocholic acid (TCA) injection (BDO plus TCA group), rats with BDO plus
tauroursodeoxycholic acid (TUDCA) injection (BDO plus TUDCA group), rats receiving a choledoco-caval shunt (CCS) operation (CCS groups), rats receiving a CCS operation plus TCA Injection (CCS plus TCA group), and rats receiving a CCS operation
plus
TUDCA injection (CCS plus TUDCA group). The TMT activities in the serum and in the hepatic subcellular fractions isolated from these experimental rats were determined. The values of Km and Vmax in this hepatic enzyme were measured.
Results: The activities of liver mitochondrial and microsomal TMTs as well as the Vmax values of TMT were found to be increased significantly in both the CCS plus TCA and the BDO plus TCA groups, compared with the CCS and BDO groups. On the
other
hand, the Km values of hepatic subcellular TMT were the same in all experimental groups. The serum TMT activity increased significantly in both the CCS plus TCA and the BDO plus TCA groups, compared with the control, CCS and BDO groups. However,
these
serum and hepatic enzyme activities were the same in the CCS plus TUDCA and the BDO plus TUDCA groups.
Conclusion: The above results suggest that TCA stimulates the biosynthesis of TMT in the liver. Also, the elevated TMT activity in the serum is thought to be caused by an increase in membrane permeability of hepatocytes from liver cell
necrosis
caused by TCA.
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