Molecular Biology and Bioinformatics Laboratory, Biological and Health Sciences Area, University West of Santa Catarina, Joaçaba, SC, Brazil.
Basic Clin Pharmacol Toxicol. 2010 Dec;107(6):965-70. doi: 10.1111/j.1742-7843.2010.00614.x.
Gender is one of the most important factors in mammalian development and response to exogenous agents. Although there is increasing evidence that health effects of toxic xenobiotics differ in prevalence or are manifested differently in male and female, the molecular mechanisms related to these events remain unclear. In order to investigate the possible influence of gender, male and female Wistar rats from the same litter were exposed to zinc chloride (5 mg/kg, i.p.) or malathion (250 mg/kg, i.p.) 24 hr prior to the analyses of biochemical parameters related to the cholinergic and glutathione-antioxidant systems in cerebral cortex and hippocampus. After treatments, acetylcholinesterase (AChE) activity was reduced in the hippocampus and cerebral cortex of male and female rats treated with malathion, but the effect was more pronounced in the male group. Glutathione reductase (GR) and γ-glutamyl-transpeptidase activities were reduced in the hippocampus of males and females and a gender-specific effect of malathion was seen for glutathione S-transferase (GST), which was decreased only in male hippocampus and cortex, and for male cortical GR. Zinc chloride treatment decreased AChE activity in male and female cerebral cortex, with no obvious effect in the hippocampus. Male-specific antioxidant-related enzyme activity reductions were seen after zinc treatment for cortical GR, GST, glutathione peroxidase and glucose-6-phosphate dehydrogenase; and hippocampal GR. These results clearly demonstrate a greater detrimental effect on antioxidant-related enzyme activities in male hippocampus and cerebral cortex when rats were acutely exposed to malathion and zinc, demonstrating that the research on gender-related differences in health effects caused by xenobiotic and/or essential elements requires further attention.
性别是哺乳动物发育和对外源物质反应的最重要因素之一。尽管越来越多的证据表明，有毒异生物质对健康的影响在流行程度上有所不同，或者在男性和女性中的表现方式不同，但与这些事件相关的分子机制仍不清楚。为了研究性别可能产生的影响，同一窝的雄性和雌性 Wistar 大鼠在接受氯化锌（5mg/kg，腹腔注射）或马拉硫磷（250mg/kg，腹腔注射）处理前 24 小时，分析与大脑皮层和海马胆碱能和谷胱甘肽抗氧化系统相关的生化参数。处理后，雄性和雌性大鼠海马和大脑皮层中的乙酰胆碱酯酶（AChE）活性均降低，但马拉硫磷处理组雄性大鼠的降低更为明显。雄性和雌性大鼠海马中的谷胱甘肽还原酶（GR）和γ-谷氨酰转肽酶活性降低，且马拉硫磷对雄性海马中的谷胱甘肽 S-转移酶（GST）产生了性别特异性影响，仅降低了雄性海马和皮层中的 GST，以及雄性大脑皮层中的 GR。氯化锌处理降低了雄性和雌性大脑皮层中的 AChE 活性，但对海马没有明显影响。锌处理后，雄性大脑皮层中的抗氧化相关酶活性降低，包括 GR、GST、谷胱甘肽过氧化物酶和葡萄糖-6-磷酸脱氢酶；以及海马中的 GR。这些结果清楚地表明，当大鼠急性暴露于马拉硫磷和锌时，雄性海马和大脑皮层中的抗氧化相关酶活性受到更大的损害，这表明需要进一步关注研究异生物质和/或必需元素对健康影响的性别差异。
