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当以长期低剂量方案给药时,内分泌干扰物与农药草甘膦的混合物会在兔肝脏中诱导氧化应激:强化现实生活风险模拟的概念。

A Mixture of Endocrine Disruptors and the Pesticide Roundup Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation.

作者信息

Vardakas Periklis, Veskoukis Aristidis S, Rossiou Danai, Gournikis Christos, Kapetanopoulou Theodora, Karzi Vasiliki, Docea Anca Oana, Tsatsakis Aristidis, Kouretas Demetrios

机构信息

Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, Greece.

Department of Nutrition and Dietetics, University of Thessaly, 42132 Trikala, Greece.

出版信息

Toxics. 2022 Apr 14;10(4):190. doi: 10.3390/toxics10040190.

Abstract

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics.

摘要

人类每天都通过长期低剂量接触外源性混合物。旨在模拟这种接触情况的研究接近现代毒理学的现实生活风险模拟(RLRS)理念。本研究的目的是调查新西兰兔连续12个月接触由七种内分泌干扰物(EDs)组成的外源性混合物、对血液和组织氧化还原状态的影响,这七种内分泌干扰物是引起人们对人类健康高度关注的化学物质,此外还包括除草剂草甘膦及其商业制剂农达。本文报道,在系统水平上,EDs混合物给药3个月时会引起血液氧化还原稳态的扰动,而在6个月和12个月时,它会激活氧化还原适应性。相反,单独接触草甘膦和农达主要会导致血液氧化还原平衡紊乱。在组织水平上,特别是在肝脏中,EDs混合物和农达的给药都会诱导氧化应激,而草甘膦则不会影响氧化应激。这些发现似乎证实了RLRS概念。事实上,在长期低剂量方案下,EDs混合物和农达的给药对肝脏的氧化还原状态产生了有害影响,肝脏是一个关键组织,在生物体对外源性物质的解毒过程中具有重要的生物学作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3896/9029199/8085d5a74655/toxics-10-00190-g001.jpg

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