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孕期对羟基苯甲酸酯(甲基和丁基)的使用:F1代睾丸的线粒体生物能量学以及睾丸和其他重要器官的抗氧化能力改变

Use of Parabens (Methyl and Butyl) during the Gestation Period: Mitochondrial Bioenergetics of the Testes and Antioxidant Capacity Alterations in Testes and Other Vital Organs of the F1 Generation.

作者信息

Oliveira Maria Manuel, Martins Fátima, Silva Mónica G, Correia Elisete, Videira Romeu, Peixoto Francisco

机构信息

Chemistry Research Centre (CQ-VR), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal.

Center for Computational and Stochastic Mathematics (CEMAT), Department of Mathematics, IST-UL, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal.

出版信息

Antioxidants (Basel). 2020 Dec 18;9(12):1302. doi: 10.3390/antiox9121302.

Abstract

Since the mid-1920s, parabens have been widely used as antimicrobial preservatives in processed foods and beverages, pharmaceuticals, and cosmetic products. Paraben use continues to generate considerable controversy, both in the general population and in the scientific community itself. The primary purpose of our study was to determine whether parabens (methyl and butyl at concentrations of 100 and 200 mg/kg body weight by subcutaneous injection) during pregnancy of adult female Wistar rats can have an impact on the F1 generation. As far as we know, we are the first to demonstrate that using parabens during pregnancy has negative repercussions on the mitochondrial bioenergetics and antioxidant activity of testicular germ cells in the F1 generation. Our study showed that there was a 48.7 and 59.8% decrease in the respiratory control index with 100 and 200 mg/kg of butylparaben, respectively. Cytochrome c oxidase activity was significantly inhibited (45 and 51%) in both groups. In addition, 200 mg/kg butylparaben promoted a marked decrease in citrate synthase activity, indicating that mitochondrial content decreased in the germ cells, especially spermatocytes and spermatids. Mitochondrial ROS production increased in groups exposed to parabens in a concentration-dependent manner, especially the butyl one (102 and 130%). The groups exposed to butylparaben showed an increase in superoxide dismutase (SOD) and catalase (CAT) activities, while glutathione reductase (GR) and glutathione -transferase (GST) decreased. With methylparaben, only differences in SOD and GR were observed; for the latter, this only occurred with the highest concentration. The glutathione (GSH)/glutathione disulfide (GSSG) ratio did not undergo any significant change. However, there was a considerable increase in hydroperoxide content in animals exposed to butylparaben, with 100 and 200 mg/kg resulting in 98.6 and 188% increase, respectively. Furthermore, several other organs also showed alterations in antioxidant capacity due to paraben use. In summary, our study demonstrates that paraben use during pregnancy will cause severe changes in the mitochondrial bioenergetics and antioxidant capacity of testicular germ cells and the antioxidant capacity of several other F1 generation organs.

摘要

自20世纪20年代中期以来,对羟基苯甲酸酯类作为抗菌防腐剂已被广泛应用于加工食品、饮料、药品和化妆品中。对羟基苯甲酸酯类的使用在普通人群和科学界内部都引发了相当大的争议。我们研究的主要目的是确定成年雌性Wistar大鼠在孕期皮下注射浓度为100和200mg/kg体重的对羟基苯甲酸甲酯和丁酯是否会对F1代产生影响。据我们所知,我们是首个证明孕期使用对羟基苯甲酸酯类会对F1代睾丸生殖细胞的线粒体生物能量学和抗氧化活性产生负面影响的研究。我们的研究表明,分别使用100和200mg/kg丁基对羟基苯甲酸酯时,呼吸控制指数分别下降了48.7%和59.8%。两组中的细胞色素c氧化酶活性均受到显著抑制(分别为45%和51%)。此外,200mg/kg丁基对羟基苯甲酸酯使柠檬酸合酶活性显著降低,表明生殖细胞,尤其是精母细胞和精子细胞中的线粒体含量减少。暴露于对羟基苯甲酸酯类的组中线粒体活性氧的产生呈浓度依赖性增加,尤其是丁基对羟基苯甲酸酯组(分别增加102%和130%)。暴露于丁基对羟基苯甲酸酯的组中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性增加,而谷胱甘肽还原酶(GR)和谷胱甘肽转移酶(GST)活性降低。对于对羟基苯甲酸甲酯,仅观察到SOD和GR存在差异;对于GR,仅在最高浓度时出现差异。谷胱甘肽(GSH)/氧化型谷胱甘肽(GSSG)比值未发生任何显著变化。然而,暴露于丁基对羟基苯甲酸酯的动物体内过氧化氢含量显著增加,100和200mg/kg分别导致增加98.6%和188%。此外,由于使用对羟基苯甲酸酯类,其他几个器官的抗氧化能力也出现了改变。总之,我们的研究表明孕期使用对羟基苯甲酸酯类会导致睾丸生殖细胞的线粒体生物能量学和抗氧化能力以及F1代其他几个器官的抗氧化能力发生严重变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2ec/7766258/598853408264/antioxidants-09-01302-g001.jpg

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