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Hepatotoxic and immunotoxic effects produced by 1,3-dibromopropane and its conjugation with glutathione in female BALB/c mice.
- Source :
-
Journal of toxicology and environmental health. Part A [J Toxicol Environ Health A] 2007 Aug; Vol. 70 (15-16), pp. 1381-90. - Publication Year :
- 2007
-
Abstract
- To determine a possible role of glutathione (GSH) conjugation in 1,3-dibromopropane (1,3-DBP)-induced hepatotoxicity and immunotoxicity, female BALB/c mice were treated orally with 1,3-DBP. Based on the liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS) analyses, two forms of S-bromopropyl GSH were observed at m/z 427.9 and 429.9 in the positive ESI spectrum with a retention time of 5.29 and 5.23 min, respectively. Following single treatment of mice with 150, 300 or 600 mg/kg 1,3-DBP for 12 hr, the amount of S-bromopropyl GSH was detected maximally in liver homogenates at 600 mg/kg 1,3-DBP. Hepatic GSH levels were significantly decreased by treatment with 1,3-DBP. In a time course study, production of S-bromopropyl GSH rose maximally 6 hr after treatment and decreased gradually thereafter. The liver weights were significantly increased by treatment with 600 mg/kg 1,3-DBP. When mice were treated orally with 600 mg/kg 1,3-DBP for 12 hr, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased by 365- and 83-fold. In addition, oral 1,3-DBP significantly suppressed the antibody response to a T-dependent antigen at 600 mg/kg 1,3-DBP. 1,3-DBP elevated hepatic levels of malondialdehyde and suppressed the activities of some hepatic enzymes involved in anti-oxidation. Taken together, the formation of GSH conjugate with 1,3-DBP may deplete cellular GSH and, subsequently, produce hepatotoxicity and immunotoxicity via damage to the cellular anti-oxidative system.
- Subjects :
- Administration, Oral
Animals
Disease Models, Animal
Female
Glutathione metabolism
Insecticides immunology
Insecticides metabolism
Mice
Mice, Inbred BALB C
Propane immunology
Propane metabolism
Propane toxicity
Spectrometry, Mass, Electrospray Ionization
Chemical and Drug Induced Liver Injury physiopathology
Glutathione drug effects
Insecticides toxicity
Liver drug effects
Metabolic Detoxication, Phase II
Propane analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1528-7394
- Volume :
- 70
- Issue :
- 15-16
- Database :
- MEDLINE
- Journal :
- Journal of toxicology and environmental health. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 17654258
- Full Text :
- https://doi.org/10.1080/15287390701434489