Franco Jeferson L, Posser Thais, Mattos Jacó J, Trevisan Rafael, Brocardo Patricia S, Rodrigues Ana Lúcia S, Leal Rodrigo B, Farina Marcelo, Marques Maria R F, Bainy Afonso C D, Dafre Alcir L
Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
Toxicol Lett. 2009 Jun 22;187(3):137-43. doi: 10.1016/j.toxlet.2009.02.015. Epub 2009 Mar 4.
Malathion toxicity has been related to the inhibition of acetylcholinesterase and induction of oxidative stress, while zinc has been shown to possess neuroprotective effects in experimental and clinical studies. In the present study the effect of zinc chloride (zinc) was addressed in adult male Wistar rats following a long-term treatment (30 days, 300mg/L in tap water ad libitum) against an acute insult caused by a single malathion exposure (250mg/kg, i.p.). Malathion produced a significant decrease in hippocampal acetylcholinesterase, as well as a decrease in the activity of several hippocampal antioxidant enzymes: glutathione reductase, glutathione S-transferase, catalase and superoxide dismutase. The pretreatment with zinc did not completely prevent acetylcholinesterase activity impairment; however, antioxidant activity was completely restored. Zinc administration significantly increased HSP60, but not HSP70, expression. The HSP60 increase suggests a novel zinc-dependent pathway, which may be related to a counteracting mechanism against malathion effects. Based on these results the following hypothesis can be presented: the published "pro-oxidative" effect of malathion may be related, among others, to compromised antioxidant defenses, while the zinc "antioxidant" action may be related to the preservation of antioxidant defenses. In conclusion, our data points to the inhibition of antioxidant enzymes as an important non-cholinergic effect of malathion, which can be rescued by oral zinc treatment.
马拉硫磷的毒性与乙酰胆碱酯酶的抑制及氧化应激的诱导有关，而锌在实验和临床研究中已显示出具有神经保护作用。在本研究中，对成年雄性Wistar大鼠进行长期治疗（30天，自来水中300mg/L，随意饮用）后，探讨氯化锌（锌）对单次腹腔注射马拉硫磷（250mg/kg）所致急性损伤的影响。马拉硫磷使海马乙酰胆碱酯酶显著降低，同时几种海马抗氧化酶的活性也降低，这些抗氧化酶包括谷胱甘肽还原酶、谷胱甘肽S-转移酶、过氧化氢酶和超氧化物歧化酶。锌预处理并未完全防止乙酰胆碱酯酶活性受损；然而，抗氧化活性完全恢复。锌给药显著增加了HSP60的表达，但未增加HSP70的表达。HSP60的增加提示了一条新的锌依赖性途径，这可能与对抗马拉硫磷作用的机制有关。基于这些结果，可以提出以下假设：已发表的马拉硫磷“促氧化”作用可能尤其与抗氧化防御受损有关，而锌的“抗氧化”作用可能与抗氧化防御的保存有关。总之，我们的数据表明抗氧化酶的抑制是马拉硫磷的一种重要的非胆碱能效应，口服锌治疗可以挽救这种效应。
