title: Time-course and molecular mechanism of hepatotoxicity induced by 1,3-dichloro-2-propanol in rats.
abstract: This study investigated the time-course of 1,3-dichloro-2-propanol (1,3-DCP)-induced hepatotoxicity and the molecular mechanism of its oxidative stress and apoptotic changes in rats. Thirty-six male rats were randomly assigned to six groups of six rats each and were administered a single oral dose of 1,3-DCP (90 mg/kg) or its vehicle. 1,3-DCP caused acute hepatic damage, as evidenced by marked increases in serum aminotransferase, alkaline phosphatase, and histopathological alterations. These functional and histopathological changes in the liver peaked at 12h after administration and then decreased progressively. Oxidative stress indices were increased significantly at 6h, peaked at 12h, and then decreased progressively. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)- and caspase-3-positive cells increased after 6h, peaked at 12 and 24h, and then decreased. The protein levels of phosphorylated mitogen-activated protein kinases (MAPKs) including p-Erk1/2 and p-JNK showed a similar trend to the numbers of TUNEL- and caspase-3-positive cells. These results indicate that 1,3-DCP increases oxidative stress, nuclear translocation of Nrf2, and expression of Nrf2-targeted genes, followed by increased functional and histopathological alterations in the liver. The increase in hepatocellular apoptosis induced by 1,3-DCP may be related to oxidative stress-mediated MAPK activation.
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea; Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeonbuk 580-185, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Og-Sung
authors.initials: OS
authors.lastname: Moon
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Won-Kee
authors.initials: WK
authors.lastname: Yoon
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: toxkim@jnu.ac.kr.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000517:alpha-Chlorohydrin / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: C033489:1,3-dichloro-2-propanol; D000517:alpha-Chlorohydrin
keywords: 1,3-Dichloro-2-propanol; Hepatotoxicity; Mechanism of action; Time-course