Roles of oxidative damage and mitochondria-mediated apoptosis in ethylbenzene-induced hepatotoxic effects in rat

• Published in: Inhalation toxicology Vol. 27; no. 1; pp. 64 - 73
• Main Authors: Zhang, Ming, Wang, Yanrang, Yang, Deyi, Zhang, Jingshu, Gu, Qing
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare USA, Inc 01.01.2015; Informa Healthcare
• Subjects: Alanine Transaminase - blood; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Aspartate Aminotransferases - blood; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Benzene Derivatives - toxicity; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase 9 - genetics; Caspase 9 - metabolism; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - genetics; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; ethylbenzene; Glutathione - metabolism; Glutathione Peroxidase - metabolism; hepatotoxicity; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver - ultrastructure; Male; Malondialdehyde - metabolism; mitochondria; Mitochondria - metabolism; Mitochondria - pathology; oxidative damage; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; rat; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Superoxide Dismutase - metabolism; oxidative damage; rat; ethylbenzene; hepatotoxicity; mitochondria; Apoptosis
• ISSN: 0895-8378; 1091-7691
• DOI: 10.3109/08958378.2014.986314

Abstract 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/m3, 4335 mg/m3 and 6500 mg/m3 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/m3 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.