Wang Qing-Shan, Xie Ke-Qin, Zhang Cui-li, Zhu Ying-Jian, Zhang Li-Ping, Guo Xin, Yu Su-fang
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, 250012, P.R. China.
Neurochem Res. 2005 Nov;30(11):1387-95. doi: 10.1007/s11064-005-8391-1.
To accurately know the time-dependent changes of the lipid peroxidation and antioxidative status for elucidating the mechanism of neuropathy induced by allyl chloride (AC), the malondialdehyde (MDA), anti-reactive oxygen species (anti-ROS), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were investigated in cerebrum, spinal cord and sciatic nerve of rats after 0, 3, 6, 9, 12 weeks of AC administration. AC was administrated to Wistar rats by gavage at a single dosage of 200 mg/kg/per dose (three times per week). Rats were sacrificed after 0, 3, 6, 9, 12 weeks of treatment, and cerebrum, spinal cord, sciatic nerves were dissected, homogenized and used for the determination of lipid peroxidation and antioxidative status. The results showed that MDA in cerebrum (112.4%) and sciatic nerve (113.1%) significantly increased (P<0.05) on third week of AC treatment and at gait score of 2, and further changes of MDA were observed after 6, 9, 12 weeks and at gait score of 3, 4. While a decrease (P<0.05) in the activities of GSH, CAT, GPx and SOD after 6, 9, 12 weeks intoxication and at gait score of 2, 3, 4 were observed in cerebrum, spinal cord and sciatic nerve. Anti-ROS activities also decreased in all three nerve tissues after 3, 6, 9, 12 weeks intoxication and at gait score of 2, 3, 4. Thus, AC intoxication was associated with elevation of lipid peroxidation and reduction of antioxidative status, and the time-dependent changes of these indexes in Wistar rats nerve tissues occurred. Sciatic nerve was the main target tissue and MDA was most sensitive among all indexes. The changes of lipid peroxidation and antioxidative status might be related to the degradation of nerve fiber and served as one of mechanisms of toxic neuropathy induced by AC.
为准确了解脂质过氧化和抗氧化状态随时间的变化,以阐明烯丙基氯(AC)诱导神经病变的机制,在给予AC 0、3、6、9、12周后,对大鼠大脑、脊髓和坐骨神经中的丙二醛(MDA)、抗活性氧(anti-ROS)、谷胱甘肽(GSH)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)进行了研究。以200mg/kg/剂量的单次剂量通过灌胃法给Wistar大鼠施用AC(每周三次)。在治疗0、3、6、9、12周后处死大鼠,解剖大脑、脊髓、坐骨神经,匀浆并用于测定脂质过氧化和抗氧化状态。结果显示,在AC治疗第三周且步态评分为2时,大脑(112.4%)和坐骨神经(113.1%)中的MDA显著增加(P<0.05),在6、9、12周后以及步态评分为3、4时观察到MDA的进一步变化。而在中毒6、9、12周后以及步态评分为2、3、4时,在大脑、脊髓和坐骨神经中观察到GSH、CAT、GPx和SOD的活性降低(P<0.05)。在中毒3、6、9、12周后以及步态评分为2、3、4时,所有三种神经组织中的抗ROS活性也降低。因此,AC中毒与脂质过氧化升高和抗氧化状态降低相关,并且在Wistar大鼠神经组织中发生了这些指标的时间依赖性变化。坐骨神经是主要靶组织,MDA在所有指标中最敏感。脂质过氧化和抗氧化状态的变化可能与神经纤维的退化有关,并作为AC诱导的中毒性神经病变的机制之一。