Hepatotoxic and immunotoxic effects produced by 1,3-dibromopropane and its conjugation with glutathione in female BALB/c mice.
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.
Lee
Sang Kyu
SK
College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
Lee
Dong Ju
DJ
Jeong
Hemin
H
Bista
Sudeep R
SR
Kang
Mi Jeong
MJ
Lee
Eung Seok
ES
Son
Jong Keun
JK
Nam
Doo Hyun
DH
Chang
Hyeun Wook
HW
Lee
Seung Ho
SH
Jahng
Yurngdong
Y
Jeong
Tae Cheon
TC
D000284:Administration, Oral; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D007306:Insecticides / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D008807:Mice, Inbred BALB C; D011407:Propane / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D021241:Spectrometry, Mass, Electrospray Ionization
D007306:Insecticides; D005978:Glutathione; D011407:Propane; C032699:1,3-dibromopropane