PMID- 25518993 OWN - NLM STAT- MEDLINE DCOM- 20150917 LR - 20161125 IS - 1091-7691 (Electronic) IS - 0895-8378 (Linking) VI - 27 IP - 1 DP - 2015 Jan TI - Roles of oxidative damage and mitochondria-mediated apoptosis in ethylbenzene-induced hepatotoxic effects in rat. PG - 64-73 LID - 10.3109/08958378.2014.986314 [doi] AB - The mechanisms underlying hepatoxic effects of ethylbenzene still remain unknown. We investigated the toxic effects of ethylbenzene on liver and explored the mechanism of mitochondria-mediated apoptosis pathway. Forty male Sprague-Dawley rats were used as an in vivo model with ethylbenzene inhalation of 0, 433.5 mg/m(3), 4335 mg/m(3) and 6500 mg/m(3) for 13 weeks. Levels of malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase were assayed. Meanwhile, the ultrastructure of hepatic tissues was observed and cell apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Furthermore, we investigated the expression levels of mRNA and protein of bax, bcl-2, cytochrome c, caspase-9 and caspase-3 in rat liver tissues. Compared with control group, the malondialdehyde levels were significantly elevated while glutathione levels and activities of glutathione peroxidase and superoxide dismutase were decreased, respectively. The mitochondria of liver appeared swollen with vacuolar structure and loss of cristae in 6500 mg/m(3) ethylbenzene-treated group, and ethylbenzene induced a significant increase in the percentage of apoptotic cells as compared to the control group. In addition, enhanced mRNA and protein expression levels of all measured genes were observed in ethylbenzene-treated groups except the decreased bcl-2 expression levels. Our results indicated that ethylbenzene may induce oxidative damage and apoptosis in rat liver. Mitochondrial-mediated pathway was involved in the apoptosis process. FAU - Zhang, Ming AU - Zhang M AD - Tianjin Centers for Disease Control and Prevention , Tianjin , P. R. China. FAU - Wang, Yanrang AU - Wang Y FAU - Yang, Deyi AU - Yang D FAU - Zhang, Jingshu AU - Zhang J FAU - Gu, Qing AU - Gu Q LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141218 PL - England TA - Inhal Toxicol JT - Inhalation toxicology JID - 8910739 RN - 0 (Bax protein, rat) RN - 0 (Benzene Derivatives) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 0 (bcl-2-Associated X Protein) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Casp9 protein, rat) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) RN - GAN16C9B8O (Glutathione) RN - L5I45M5G0O (ethylbenzene) SB - IM MH - Alanine Transaminase/blood MH - Animals MH - Apoptosis/*drug effects/physiology MH - Aspartate Aminotransferases/blood MH - Benzene Derivatives/*toxicity MH - Caspase 3/genetics/metabolism MH - Caspase 9/genetics/metabolism MH - Chemical and Drug Induced Liver Injury/*etiology/genetics/metabolism/pathology MH - Glutathione/metabolism MH - Glutathione Peroxidase/metabolism MH - Liver/drug effects/metabolism/pathology/ultrastructure MH - Male MH - Malondialdehyde/metabolism MH - Mitochondria/*metabolism/pathology MH - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism MH - RNA, Messenger/metabolism MH - Rats, Sprague-Dawley MH - Superoxide Dismutase/metabolism MH - bcl-2-Associated X Protein/genetics/metabolism OTO - NOTNLM OT - Apoptosis OT - ethylbenzene OT - hepatotoxicity OT - mitochondria OT - oxidative damage OT - rat EDAT- 2014/12/19 06:00 MHDA- 2015/09/18 06:00 CRDT- 2014/12/19 06:00 PHST- 2014/12/19 06:00 [entrez] PHST- 2014/12/19 06:00 [pubmed] PHST- 2015/09/18 06:00 [medline] AID - 10.3109/08958378.2014.986314 [doi] PST - ppublish SO - Inhal Toxicol. 2015 Jan;27(1):64-73. doi: 10.3109/08958378.2014.986314. Epub 2014 Dec 18.