• Biomedical Science Letters
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• v.11 no.1
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• pp.37-43
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• 2005

The possible mechanisms of increased aryl sulfotransferase (AST) isozymes activities in cholestatic rat liver were studied. Hepatic AST-I, II and -III, IV activities were determined from the experimental rats with common bile duct ligation (CBDL). The Michaelis-Menten constants in these hepatic enzymes were also measured. The activities of mitochondrial AST-I, II and -III, IV, and microsomal AST-III, IV as well as their Vmax values were found to be increased significantly in CBDL plus taurocholic acid (TCA) injected group than in the control group, such as CBDL alone groups. However, their Km values in the experimental groups did not vary. The results suggest that TCA stimulates biosynthesis of the AST in the liver.

• Biomedical Science Letters
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• v.11 no.4
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• pp.503-508
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• 2005

Possible mechanisms of increased serum aryl sulfotransferase (AST) isozyme activities in cholestatic rats were studied. Serum AST-I, II and -III, IV isozymes activities were determined from the experimental rats with common bile duct ligation (CBDL) or choledocho-caval shunt (CCS). The activities of serum AST-I, II and -III, IV isozymes were found to be increased significantly in both the CCS plus taurocholic acid (TCA) injected group, and the CBDL plus TCA group than those in each control group, such as CCS or CBDL alone groups. The above results suggest that the elevated serum AST most likely due to increased hepatocyte membrane permeability caused by TCA mediated liver cell necrosis.

• Nutritional Sciences
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• v.9 no.1
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• pp.29-34
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• 2006

Purified rat liver aryl sulfotransferase IV (AST IV) was found to be inhibited in vitro by zinc, copper, cadmium and terbium. Among these four elements, zinc, copper and cadmium were all strongly inhibitory to the AST IV activity at very low concentrations (2.5 $\mu$M to 0.025 $\mu$M). In rat liver cytosol, zinc, copper and cadmium at 25 $\mu$M to 0.025 $\mu$M also decreased the AST IV activity to $50\%$ of the controls. In order to assess the possible effects of these metals on the AST IV activity recovery pattern in vivo, studies on the relationship between these minerals and dietary 2-acetylaminofluorene were conducted. Total of forty rats were fed one of five diets for 6 weeks: diet 1, Control diet plus 2-acetlyaminofluorene ($0.05\%$); diet 2, zinc-deficient diet plus 2-acetlyaminofluorene; diet 3, zinc-supplement diet plus 2-acetylaminofluorene; diet 4, copper-supplement diet plus 2-acetylaminofluorene; diet 5, cadmium-supplement diet plus 2-acetylaminofluorene. Half of the rats from each diet were changed to individual diet after 3 weeks of 2-acetylaminofluorene feeding. Placement of rats on the control diet following one cycle of 2-acetylaminofluorene feeding of 3 weeks without 2-acetylaminofluorene resulted in nearly full recovery of AST IV activity within 3 or 4 weeks. However, the rats fed diets that supplemented with zinc, copper or cadmium without 2-acetylaminofluorene showed a new pattern of lowered AST IV activity as early as the first cycle. Also, lowering in cytosolic AST IV contents was appeared in the livers from the rats, following one cycle of 2-acetylaminofluorene feeding of 3 weeks, fed one of the diets that supplemented with copper, cadmium or zinc without 2-acetylaminofluorene for ensuing 3 weeks.

• Nutritional Sciences
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• v.9 no.1
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• pp.20-28
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• 2006

Aryl sulfotransferase (AST) IV is a liver enzyme involved in detoxication and has been shown to be susceptible to down regulation by a number of hepatotoxic xenobiotics. Studies presented here to investigate the ability of biological and non-biological divalent metal cations on AST IV activity showed that AST IV was strongly inhibited following in vitro or in vivo exposure to. Zn ( II ), Co ( II ) or Cd ( II ). It was found that $0.025\sim$2.5 uM of these metal ions were sufficient to cause $50\%$ of inhibition in vitro in purified AST IV and $0.25\sim$25 uM of these metal ions in liver cytosolic fractions. For the in vivo study, 1,000 mg Cu ( II )/kg, 2,000 mg Zn ( II )/kg or 250 mg Cd( II )/kg was added to individual diets and administered to three (3) group; of mts over a 7 week period The Co ( II )-supplemented diet produced no apparent change in rat growth rate and resulted in 30-fold increase in liver cytotolic Cu ( II ) levels, suggesting that elevated levels of Cu ( II ) ion in the liver were responsible for the loss of AST IV activity. In contrast, the Zn ( II )-supplemented diet caused a decrease in rat growth rates and resulted in zero increase in liver Zn ( II ) levels, which suggested an indirect inhibition mechanism was caused by Zn ( II ) in the liver. Rats were fed the Cd-supplemented diet also displayed a decrease in growth rate with little or no change in liver Cu ( II ) or Zn ( II ) levels. When the liver cytosols of mts from the metal ion diets were immunochemically analyzed for the AST IV and albumin contents, no significant changes were observed in albumin levels. However, AST IV contents in the cytosols of mts fed the Zn ( II )-supplemented diets showed a slight decrease in amount These results showed that AST IV activity in vitro and in vivo can be inhibited by Co ( II ), Zn ( II ), and Cd ( II ) by apparently different mechanisms. The immediate response to a Zn injection showed a decrease in AST IV activity but not in the AST IV content in liver cytosol. These mechanisms appeared to involve direct actions of the metal ion on AST IV activity and indirect actions affecting AST IV amount.