| Objective: Acrylonitrile (Acrylonitril, AN) is an important raw material in organic synthesis industry, widely used in synthesis of acrylic fibers, nitrile rubber, ABS engineering plastics, synthetic resin, etc. In recent years, with rapid development and expansion of AN industry, occupational and daily life exposure significantly increased, Thus the protection of human beings exposed to AN, much attention has been paid to its toxicity, especially neurotoxicity. Therefore,it is necessary to explore the mechanism of neurotoxicity of AN and look for effective chemopreventive agents against AN toxicity. In this study, based on the acute and subacute experiments, by evaluation of biomarkers of oxidative stress, energy metabolism and inflammmation, the protection of Curcumin, a phytochemical extracted from Curcuma longa L. against AN neurotoxicity was explored. And it was hoped that the obtained findings will be useful to development of health food products for occupational protection.Methods: In acute experiments, twenty-eight adult healthy male Sprague-Dawley (SD) rats were randomly divided into four groups according to their body weights (seven rats in each)control group, AN group, AN following 50mg/kgCur pretreatment group and AN following 100mg/kgCur pretreatment group. The rats were orally administered curcumin at doses of 0 (olive oil control), 50 or 100 mg/kg bodyweight daily for 7 consecutive days. Two hours after the last dose of curcumin, rats received an intraperitoneal injection of 50mg AN/kg body weight. In subacute experiments, twenty-eight adult healthy male SD rats were randomly divided into four groups (seven rats in each). control group, Cur group,AN group and AN following 100mg/kgCur pretreatment group(Cur+AN). The rats were orally administered curcumin at doses of 0 (olive oil control), 100 mg/kg body weight daily, two hours after the dose of curcumin, rats received an intraperitoneal injection of 50mg AN/kg body weight for 14 consecutive days. Neurotoxicity was assessed by behavioral observations, the reduced glutathione levels (GSH), glutathione lipid peroxidation (MDA), catalase(CAT) and superoxide dismutase(SOD) activity in the brain and liver. The cytochrome c oxidase activity in brain and liver, CN~- content in rat brain, The activities of CYP2E1, CYP2E1 gene, CYP2E1 protein in the liver and histological changes were detected.Results: Acute experiment:①Behavioral observations showed that all AN-treated animals exhibited similar pattern of cholinomimetic signs.②A significant increase in levels of MDA was observed in the AN-treated group both in the brain and liver compared with the control group(38.6% and 10.8% respectively), These increases were accompanied by asignificant decrease in GSH content (38.6% and 70.5 %respectively)and a significant reduction in CAT activity in the same tissues. Pretreatment with curcumin reversed the AN-induced effects, reducing the levels of MDA and enhancing CAT activity and increasing reduced GSH content both in the brain and liver. At 100 mg/kg curcumin, the brain level of GSH returned to 83.2% of the control level, whereas hepatic GSH recovery was only 46.6%.③AN treatment significantly reduced thecytochrome c oxidase activity in the brain and liver compared with the control group, and these effects were significantly mitigated by 100 mg/kg curcumin pretreatment both in the brain and liver. The extents of recovery of activity of cytochrome c oxidase upon curcumin pretreatment in the brain was relatively higher compared with the liver, reaching approximately 75% and 58% of the control values, for brain and liver, respectively.④The hepatic CYP2E1 activity in the control and the various treatment groups. Neither the change between the AN alone and the control group, nor changes between the AN alone and the ANwith curcumin pretreatment groups were statistically significant.Subacute experiment:①Twenty minuntes later, the cholinomimetic signs, such as salivation or lacrimation and labored breathing, were observed for in AN group rats, and after about one hour, the previous symptoms disappeared gradually, the effects were significantly mitigated by curcumin pretreatment.②A significant increase in levels of MDA was observed in the AN-treated group both in the brain and liver compared with the control group, These increases were accompanied by asignificant decrease in GSH content and a significant reduction in CAT activity (54.3% and 10.2% respectively)in the same tissues. SOD activity in the brain and liver was reduced upon AN treatment, a significant decrease in SOD activity in the brain compared with controls. Pretreatment with curcumin reversed the AN-induced effects, reducing the levels of MDA and enhancing CAT activity and increasing reduced GSH content both in the brain and liver, enhancing SOD activity in the brain. Compared with the AN group, levels of MDA was significantly decreased both in brains and livers of rats in the Cur+AN group ( 33.9% and25.2% respectively). Compared with the AN group, CAT activity was significantly increased both in brains and livers of rats in the Cur+AN group (68.1% and 17.2% respectively).③A significant increase in levels of CHE was observed in the AN-treated group both in the brain compared with the control group, Pretreatment with curcumin reversed the AN-induced effects.④The activities of CYP2E1 in each group showed no significant difference by Western blot and RT-PCR detection.Conclusion:The present study provides direct evidence for the involvement of curcumin in neuroprotection against oxidative stress. Curcumin may also terminate lipid peroxidation by induction ofenzymatic and non-enzymatic antioxidants, such as GSH, SOD and CAT. curcumin is a safe and effective plants to prevent oxidative damage and related toxins, the way that curcumin pretreatment protects against acrylonitrile-induced oxidative damage, may not be the means by changing the level of CYP2E1. |
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