Wang Qing-Shan, Zhang Cui-Li, Zhao Xiu-Lan, Yu Su-Fang, Xie Ke-Qin
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
Toxicology. 2006 Oct 3;227(1-2):36-44. doi: 10.1016/j.tox.2006.07.006. Epub 2006 Jul 10.
Chronic exposure to allyl chloride (AC) is known to produce a central-peripheral distal axonopathy. To access the biomarker of exposure and elucidate the mechanism of neuropathy induced by AC, we performed a longitudinal observational study of malondialdehyde (MDA), anti-reactive oxygen species (anti-ROS), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in rats serum and sciatic nerve after 0, 3, 6, 9 and 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 and 12 weeks of AC treatment, serum and sciatic nerves were quickly collected at 4 degrees C. The results showed that MDA levels in serum (115.4 and 126.2%) and sciatic nerve (130.5 and 145.3%) significantly increased (p<0.05) on 3rd week of AC treatment and at gait score of 2, and further changes of MDA levels were observed after 6, 9 and 12 weeks and at gait score of 3 and 4. While a decrease (p<0.05) in the activities of CAT on 6th week of AC intoxication and at gait score of 2 was observed in serum (81.2 and 72.8%) and sciatic nerve (71.7 and 70.7%). The other antioxidants also decreased in serum and sciatic nerve after 3, 6 and 9, 12 weeks' intoxication and at gait score of 2, 3 and 4. Significant (p<0.05) positive correlations were observed between serum and sciatic nerve in MDA levels (r=0.9162 and 0.9551, respectively) and CAT (r=0.9410 and 0.9557, respectively) activities as time went on and symptoms developed. 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' serum and sciatic nerve occurred. The misbalance of lipid peroxidation and antioxidation status might be one of mechanisms of toxic neuropathy induced by AC. MDA and CAT could be served as the biomarkers of AC exposure to afford the early diagnosis of AC-induced toxic neuropathy.
已知长期接触烯丙基氯（AC）会导致中枢 - 外周远端轴索性神经病。为了探寻接触生物标志物并阐明AC所致神经病变的机制，我们对Wistar大鼠在给予AC 0、3、6、9和12周后血清和坐骨神经中的丙二醛（MDA）、抗活性氧（抗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）进行了纵向观察研究。以200 mg/kg/剂量的单次剂量经口灌胃给予Wistar大鼠AC（每周三次）。在AC治疗0、3、6、9和12周后处死大鼠，在4℃下迅速收集血清和坐骨神经。结果显示，在AC治疗第3周且步态评分为2时，血清中MDA水平（分别升高115.4%和126.2%）和坐骨神经中MDA水平（分别升高130.5%和145.3%）显著升高（p<0.05），并且在6、9和12周以及步态评分为3和4时观察到MDA水平的进一步变化。而在AC中毒第6周且步态评分为2时，血清（分别下降至81.2%和72.8%）和坐骨神经（分别下降至71.7%和70.7%）中CAT活性下降（p<0.05）。在中毒3、6以及9、12周后且步态评分为2、3和4时，血清和坐骨神经中的其他抗氧化剂也下降。随着时间推移和症状发展，血清和坐骨神经中MDA水平（分别为r = 0.9162和0.9551）以及CAT活性（分别为r = 0.9410和0.9557）之间观察到显著的（p<0.05）正相关。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Wistar大鼠血清和坐骨神经中这些指标出现了时间依赖性变化。脂质过氧化与抗氧化状态的失衡可能是AC所致中毒性神经病变的机制之一。MDA和CAT可作为AC接触的生物标志物，为AC所致中毒性神经病变的早期诊断提供依据。
