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

- Tolerance to dichloroacetonitrile (DCAN)-induced neurotoxicity in diabetic rats.
- The median survival time and total lethal time in DCAN-exposed diabetic rats were prolonged.
- Diabetes did not aggravate DCAN-induced motor impairment and anxiety like behaviour.
- Diabetes slowed down pathological pace of DCAN-induced mitochondrial dysfunction.
- Diabetes had no significant effect on DCAN-induced oxidative damage.

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.

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