Role of Metabolism In 1-Bromopropane-Induced Hepatotoxicity in Mice

Lee, Sang Kyu; Kang, Mi Jeong; Jeon, Tae Won; Ha, Hyun Woo; Yoo, Jeong-Ah; Ko, Gyu Sub; Kang, Wonku; Jeong, Hye Gwang; Lyoo, Won Seok; Jeong, Tae Cheon

doi:10.1080/15287394.2010.511546

Cited by 14 publications

(10 citation statements)

References 24 publications

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“…Thus, L-cysteine supplementation apparently protects hepatic cells against induction by D-GalN. Similarly Lee et al (33) reported that an increase in the serum MDA level caused by 1-bromopropane, which induces hepatotoxicity, was prevented by treatment with NAC. Cysteine inhibited LDL oxidation, which induced generation of serum lipid peroxides, by reduction of Cu 2+ to Cu + (34).…”

Section: Serum and Liver Gsh And Lipid Peroxide Analysesmentioning

confidence: 89%

Dietary l-cysteine inhibits d-galactosamine-induced acute liver injury in rats

Lee

Han

Yabuki

et al. 2015

Food Sci Biotechnol

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The effects of L-cysteine (1 and 2%) on the antioxidative system were examined in rats with Dgalactosamine (D-GalN)-induced injury. These rats showed increases in serum antioxidative enzyme and hepatic thiobarbituric acid reactive substances (TBARS) activities, with decreased hepatic/serum glutathione (GSH) levels and GSH-related enzyme activities. However, L-cysteine supplementation resulted in a decrease of hepatic TBARS levels, and increased catalase and serum GSH levels. The activities of serum enzymes in rats receiving 2% L-cysteine were significantly (p<0.05) lower than in D-GalN-injected group rats, and similar to levels in control group rats without acute liver injury. In addition, 2% L-cysteine increased the glutathione reductase activity and decreased the serum TBARS level in liver injury group rats. Dietary L-cysteine, especially at a 2% level, exerts a hepatoprotective effect by alteration of the GSH level and antioxidative enzyme activities.

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Section: Serum and Liver Gsh And Lipid Peroxide Analysesmentioning

confidence: 89%

Dietary l-cysteine inhibits d-galactosamine-induced acute liver injury in rats

Lee

Han

Yabuki

et al. 2015

Food Sci Biotechnol

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“…The results suggest 1-BP concentration in blood might directly indicate the current exposure level in the rodent model, but may also reflect the cumulative exposure in human. So far, 2 potential metabolic pathways were studied and correlated with 1-BP reproductive toxicity and hepatotoxicity (Garner et al, 2007;Lee et al, 2010). CYP2E1-dependent oxidation and GSH conjugation were the 2 critical metabolic pathways and produced the major 1-BP metabolites detected in the urine samples.…”

Section: Discussionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling for 1-Bromopropane in F344 Rats Using Gas Uptake Inhalation Experiments

et al. 2015

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1-Bromopropane (1-BP) was introduced into the workplace as an alternative to ozone-depleting solvents and increasingly used in manufacturing industry. The potential exposure to 1-BP and the current reports of adverse effects associated with occupational exposure to high levels of 1-BP have increased the need to understand the mechanism of 1-BP toxicity in animal models as a mean of understanding risk in workers. Physiologically based pharmacokinetic (PBPK) model for 1-BP has been developed to examine 2 metabolic pathway assumptions for gas-uptake inhalation study. Based on previous gas-uptake experiments in the Fischer 344 rat, the PBPK model was developed by simulating the 1-BP concentration in a closed chamber. In the model, we tested the hypothesis that metabolism responsibilities were shared by the p450 CYP2E1 and glutathione (GSH) conjugation. The results showed that 2 metabolic pathways adequately simulated 1-BP closed chamber concentration. Furthermore, the above model was tested by simulating the gas-uptake data of the female rats pretreated with 1-aminobenzotrizole, a general P450 suicide inhibitor, or d,l-buthionine (S,R)-sulfoximine, an inhibitor of GSH synthesis, prior to exposure to 800 ppm 1-BP. The comparative investigation on the metabolic pathway of 1-BP through the PBPK modeling in both sexes provides critical information for understanding the role of p450 and GSH in the metabolism of 1-BP and eventually helps to quantitatively extrapolate current animal studies to human.

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“…Because 1-BB could also be metabolized by CYPs (James et al , 1968) , certain phase I metabolite (s) might contribute to 1-BB-induced hepatotoxicity. For example, we recently reported that phase I metabolism of 1-BP by CYPs, at least in partial, might contribute to its toxicity, in addition to oxidative stress by GSH depletion via conjugate formation with GSH (Lee et al , 2010) .…”

Section: Discussionmentioning

confidence: 99%

Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice

Lee¹,

Lee²,

Jeon³

et al. 2010

Toxicological Research

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Halogenated organic compounds, such as 1-bromobutane (1-BB) , have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

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Role of Metabolism In 1-Bromopropane-Induced Hepatotoxicity in Mice

Cited by 14 publications

References 24 publications

Dietary l-cysteine inhibits d-galactosamine-induced acute liver injury in rats

Dietary l-cysteine inhibits d-galactosamine-induced acute liver injury in rats

Physiologically Based Pharmacokinetic Modeling for 1-Bromopropane in F344 Rats Using Gas Uptake Inhalation Experiments

Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice

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