Hepatotoxic effect of 1-bromopropane and its conjugation with glutathione in male ICR mice.
The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-propyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electrospray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.
Lee
Sang Kyu
SK
College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Jo
Sang Wook
SW
Jeon
Tae Won
TW
Jun
In Hye
IH
Jin
Chun Hua
CH
Kim
Ghee Hwan
GH
Lee
Dong Ju
DJ
Kim
Tae-Oh
TO
Lee
Eung-Seok
ES
Jeong
Tae Cheon
TC
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
D006842:Hydrocarbons, Brominated; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C118559:1-bromopropane