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ABSTRACT The aim of this study was to explore the roles of cytochrome P450 2E1 (CYP2E1) in 1,2-dichloroethane (1,2-DCE)-induced liver damage. Two parts were included in this study: first, effect of 1,2-DCE on microsomal expression of CYP2E1, and second, potential of an inhibitor of CYP2E1 to reduce 1,2-DCE-induced liver damage. In part one, mice were exposed to 0, 0.225, 0.45, or 0.9 g/m3 1,2-DCE for 10 days, 3.5 h per day through static inhalation. In part two, mice were divided into blank control, solvent control, inhibitor control, 1,2-DCE-poisoned group, and low or high intervention group. In part one, compared to the control, serum alanine aminotransferase (ALT) activities and hepatic malondialdehyde (MDA) levels in 0.9 g/m3 1,2-DCE group, and microsomal CYP2E1 protein expression and activity in both 0.45 and 0.9 g/m3 1,2-DCE groups increased significantly; conversely, hepatic nonprotein sulfhydryl (NPSH) levels in both 0.45 and 0.9 g/m3 1,2-DCE groups and hepatic SOD activities in 0.9 g/m3 1,2-DCE group decreased significantly. In part two, microsomal CYP2E1 protein expression and activity decreased significantly in both low and high intervention groups compared to 1,2-DCE-poisoned group. Along with the changes of CYP2E1, hepatic MDA levels and serum ALT activities decreased; conversely, hepatic NPSH levels and SOD activities increased significantly in high intervention group. Taken together, our results suggested that 1,2-DCE could enhance CYP2E1 protein expression and enzymatic activity, which could cause oxidative damage in liver, serving as an important mechanism underlying 1,2-DCE-induced liver damage. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1430-1438, 2016. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the risk from exposure to arsenate (iAsV) or arsenite (iAsIII) at the early life. Mother mice were exposed to equimolar dose of iAsV and iAsIII via drinking water during gestation and lactation. Their offspring continually drank the same water after weaning. Levels of speciated arsenic in both liver and brain were analyzed by hydride generation of volatile arsines and atomic absorption spectrophotometry (HG-AAS). In the liver, inorganic arsenic (iAs) levels significantly increased from postnatal day (PND) 15, and those on PND 35 were significantly higher than on PND 15 and 21 in iAsIII exposed mice, but iAs levels did not significantly differ until PND 35 in iAsV exposed mice; Furthermore, all speciated arsenic levels on PND 35 and dimethylarsinic acid (DMA) levels on PND 1 were significantly higher in iAsIII exposed mice than those in iAsV exposed mice. In the brain, iAs levels increased significantly on PND 21, but those declined sharply on PND 35 in either iAsIII or iAsV exposed mice, however the mean difference between the two exposure groups was not significant; whereas DMA levels in iAsIII exposed mice were significantly higher than those in iAsV exposed mice on both PND 1 and 35. In conclusion, findings from this study suggested that iAsIII was preferentially accumulated into liver, and expected to result in more efficient methylation capacity than iAsV; either iAsV or iAsIII might be accumulated in the brain readily, when immature blood brain barrier can not limit it into brain. Hence, exposure to either iAsV or iAsIII at the early life may increase the risk of iAs exposure in the brain. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 797-803, 2014. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the effects of exogenous methionine (Met) on arsenic burden and metabolism of nitric oxide (NO) in the brain of mice exposed to arsenite via drinking water. Mice were exposed to sodium arsenite through drinking water contaminated with 50 mg/L arsenic for four consecutive weeks, and treated intraperitoneally with saline solution, 100 mg/kg body weight (b.w), 200 mg/kg b.w or 400 mg/kg b.w of Met, respectively at the fourth week. Levels of inorganic arsenic (iAs), monomethylarsenic acid (MMAs), and dimethylarsenic acid (DMAs) in the liver, blood and brain were determined by method of hydride generation coupled with atomic absorption spectrophotometry. Nitric oxide synthase (NOS) activities and NO levels in the brain were determined by colorimetric method. Compared with mice exposed to arsenite alone, administration of Met increased significantly the primary methylation ratio in the liver, which resulted in decrease of percent iAs and increase of percent DMAs in the liver, and decrease of iAs, MMAs and total arsenic levels (TAs) in the blood and DMAs and TAs in the brain. NOS activities and NO levels in the brain of mice exposed to arsenite alone were significantly lower than those in control, however administration of Met could increase significantly NO levels. Findings from this study suggested that exogenous Met could benefit the primary arsenic methylation in the liver, which might increase the production of methylated arsenicals and facilitate arsenic excretion. As a consequence, arsenic burden in both blood and brain was reduced, and toxic effects on NO metabolism in the brain were ameliorated. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2012. [ABSTRACT FROM AUTHOR]

Objective: To explore the expression of CYP2E1 in the liver of mice and its effects on liver injury induced by 1,2-dichloroethane (1, 2-DCE)., Methods: (1) Thirty-two female mice were randomly divided into four groups, which were control group, low dose group, medium dose group and high dose group. Mice were exposed to 1,2-DCE through respiratory for 4 h per day for 10 days. At the end of exposure, the mice were sacrificed, their blood and liver were collected rapidly. Pathological analysis was examined. Activity of ALT and AST in serum and activity of CYP2E1 in liver were mice were randomly divided into six groups, ie simple control group, corn oil control group, inhibitor control group, simple poisonous group, low and high dose diallyl sulfide (DAS) intervention groups. Mice were treated orally with DAS in corn oil 4 hours before 1, 2-DCE exposure. The examination indicators were as aforementioned., Results: (1) Compared to control group, activity of ALT in serum of mice in the high dose group and expression of CYP2E1 in the liver of mice in medium and high dose group increased significantly. In addition, the histological observation suggested obvious liver damage in medium and high dose group. (2) CYP2E1 protein expression and activity in liver and ALT in serum decreased significantly in DAS-intervention groups compared to simple poisonous group. Along with the changes of CYP2E1 and ALT, pathological changes of liver damage was better., Conclusion: Our results suggested that expression of CYP2E1 and oxidative damage in the liver could be induced by 1,2-DCE exposure, and CYP2E1 inhibitors can reduce the hepatic tissue damage caused by DCE.

We hypothesized that chronic exposure to arsenic would deplete the reduced glutathione (GSH) and methionine in vivo, thereby impair the methylation capacity of inorganic arsenic (iAs) ingested. Our experiment was designed to explore the effects of exogenous GSH and methionine on arsenic methylation in mice exposed to arsenite via drinking water. Levels of iAs, monomethylarsenic acid (MMAs), and dimethylarsenic acid (DMAs) in the liver and blood were determined by the method of hydride generation coupled with atomic absorption spectrophotometry. Compared with mice exposed to arsenite alone, administration of GSH or methionine increased the secondary methylation index in the liver and primary methylation index in the blood, which resulted in the consequent increase of DMAs percent and decrease of iAs percent in the blood. Moreover, administration of GSH resulted in the increase of DMAs percent in the liver and total arsenic in the blood. Increase of total arsenic in the blood was mainly due to the increase of DMAs. Findings from the present study suggested that administration of GSH or methionine might potentiate the methylation capacity of arsenic in both liver and extrahepatic tissues, which may facilitate the excretion of arsenic and decrease arsenic related toxicities in the body.