Tolerance to dichloroacetonitrile-induced neurotoxicity in streptozotocin-induced diabetic rats

作者：Li, Fang^*; Dong, Ying; Shen, Haijun; Lu, Rongzhu; Yin, Siqi; Tian, Weihong; Wang, Suhua; Xing, Guangwei

来源：Environmental Toxicology and Pharmacology, 2017, 56: 61-67.

DOI：10.1016/j.etap.2017.08.037

• Diabetes mellitus
• Nitrogenous disinfection by-products
• Dichloroacetonitrile
• Nerve behaviour
• Oxidative stress
• Mitochondrial dysfunction

Diabetes mellitus has potential to alter the toxicity of hazardous chemicals. Dichloroacetonitrile (DCAN) is one of high-risk nitrogenous disinfection by-products. This study evaluated the neurotoxicity of DCAN (11, 44 and 88 mg/kg) in normoglycaemic and streptozotocin (STZ)-induced diabetic rats via orally for 28 days. STZ diabetes prolonged the median survival time and total lethal time after DCAN (88 mg/kg) exposure when compared with that observed in normoglycaemic rats. DCAN altered motor activity and induced anxiety behaviour in normoglycaemic rats; but it did not exaggerate behavioural changes in STZ diabetic rats. DCAN induced brain oxidative damage by compensatory increase glutathione content and decrease malonaldehyde levels; but it did not induce oxidative damage in diabetic rats. STZ diabetes slowed down the pathological pace of DCAN-induced brain mitochondrial dysfunction by decreasing reactive oxygen species and increasing cytochrome C oxidase activity. In conclusion, the present study indicated that STZ diabetic rats are resistant to DCAN-induced neurotoxicity at the dosage and with the dosage schedule in 28-day subacute toxicity test.

• 出版日期2017-12
• 单位江苏大学