Wang_2010_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_28_810

OBJECTIVE: To investigate the influence of ethylbenzene on oxidative damage, ultrastructure and the expressions of apoptosis-related genes in the rat brain tissues. METHODS: Four groups of 10 males of Sprague-Dawley rats were allocated randomly, and inhaled daily with different doses of ethylbenzene: 0, 433.5 mg/m(3), 4335.0 mg/m(3), and 6500.0 mg/m(3) 6 h daily, 5 days per week for 13 weeks. The contents of glutathione (GSH) and malondialdehyde (MDA) and activity of acetylcholinesterase (AChE) were assayed, respectively. The ultrastructure of brain tissues was observed via electron microscope. The gene expression levels of Bax, Bcl-2, cytochrome C, caspase-9 and caspase-3 in brain tissues were measured by real-time polymerase chain reaction (PCR), respectively. RESULTS: The contents of MDA [(2.03 +/- 0.56), (4.17 +/- 1.31) nmol/mg pro] in the brain tissues of 4335.0 mg/m(3) and 6500.0 mg/m(3) ethylbenzene-treated groups were significantly higher than that [(1.08 +/- 0.26) nmol/mg pro] in the control group (P < 0.05), while AChE activities [(0.321 +/- 0.066), (0.276 +/- 0.031), (0.202 +/- 0.041) U/mg] and GSH contents [(35.19 +/- 15.08), (33.42 +/- 15.32), (27.99 +/- 7.53) mg/g pro] in all ethylbenzene-treated groups were remarkably depressed (P < 0.05, P < 0.05, respectively). After 6500.0 mg/m(3) ethylbenzene inhalation, the nucleolus exhibit demilune with decreased mitochondria. Electrondense of myelin occurred in the injured nerve, ascribing to lipid peroxidationed membrane. The gene expression level of Bax in brain tissue of 4335.0 mg/m(3) and 6500.0 mg/m(3) ethylbenzene-treated group was significantly higher than that in the control group (P < 0.05). Compared with the control group, the gene expression levels of cytochrome C, caspase-9 and caspase-3 in all ethylbenzene-treated groups were enhanced (P < 0.05, P < 0.05, respectively), while bcl-2 gene expression levels in all ethylbenzene-treated groups were decreased (P < 0.05). CONCLUSION: Ethylbenzene can induce oxidative damage and apoptosis in brain tissues. The apoptotic mechanism might be involved with up-regulation of Bax, cytochrome C, caspase-9 and caspase-3, as well as restraint of Bcl-2.