Kumar M R, Reddy G R
1 Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
Hum Exp Toxicol. 2018 Mar;37(3):295-308. doi: 10.1177/0960327117698540. Epub 2017 Mar 23.
This study was planned to determine arsenic (As) (10 mg/kg body weight given through oral gavage) induced behavioral and cholinergic perturbations in three different age groups of rats; young (postnatal day 21), adult (3 months), and aged (18 months) at 7 days post-acute exposure ( n = 6 for each of the four groups of all three age points). Further, we also evaluated the ameliorative effect of essential metal zinc (Zn; 0.02% through drinking water) and an antioxidant, α-tocopherol (vitamin E; 125 mg/kg body weight through oral gavage) against As-induced neurotoxicity. As exposure showed significant alterations in behavioral functions (open-field behavior, total locomotor activity, grip strength, exploratory behavior, and water maze learning). Cholinergic studies in three brain regions (cerebral cortex, cerebellum, and hippocampus) of different age groups also showed significant increase in acetylcholine levels and a decrease in acetylcholinesterase activity. These effects were more pronounced in hippocampus followed by cerebral cortex and cerebellum. Among the three different age points, aged animals were found to be more vulnerable to the As-induced toxicity as compared to young and adult animals suggesting that As neurotoxicity is age dependent. These As-induced alterations were significantly reversed following supplementation with Zn or vitamin E. However, vitamin E was found to elicit greater protection as compared to Zn in restoring the altered behavioral and cholinergic perturbations, providing evidence for As-induced oxidative damage.
本研究旨在确定急性暴露7天后，砷（As，经口灌胃给予10mg/kg体重）对三组不同年龄大鼠（幼龄，出生后第21天；成年，3个月；老龄，18个月）行为和胆碱能系统的影响（每组三个年龄点各四组，每组n = 6）。此外，我们还评估了必需金属锌（Zn，通过饮水给予0.02%）和抗氧化剂α-生育酚（维生素E，经口灌胃给予125mg/kg体重）对砷诱导的神经毒性的改善作用。砷暴露导致行为功能（旷场行为、总运动活动、握力、探索行为和水迷宫学习）发生显著改变。对不同年龄组三个脑区（大脑皮层、小脑和海马体）的胆碱能研究还显示，乙酰胆碱水平显著升高，乙酰胆碱酯酶活性降低。这些影响在海马体中最为明显，其次是大脑皮层和小脑。在三个不同年龄点中，与幼龄和成年动物相比，老龄动物被发现对砷诱导的毒性更敏感，这表明砷神经毒性具有年龄依赖性。补充锌或维生素E后，这些砷诱导的改变得到显著逆转。然而，在恢复行为和胆碱能紊乱方面，维生素E比锌具有更大的保护作用，这为砷诱导的氧化损伤提供了证据。
