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亚急性锰中毒的性别差异:成年 Wistar 大鼠外周器官的氧化参数和金属沉积。

Sex differences in subacute manganese intoxication: Oxidative parameters and metal deposition in peripheral organs of adult Wistar rats.

机构信息

Programa de Pós-Graduação em Biociências e Saúde (PPGBS), Área de Ciências da Vida e Saúde, Universidade do Oeste de Santa Catarina (UNOESC), Campus de Joaçaba, SC, Brazil.

Graduação em Ciências Biológicas, Área de Ciências da Vida e Saúde, Universidade do Oeste de Santa Catarina (UNOESC), Campus de Joaçaba, SC, Brazil.

出版信息

Regul Toxicol Pharmacol. 2019 Jun;104:98-107. doi: 10.1016/j.yrtph.2019.03.005. Epub 2019 Mar 13.

DOI:10.1016/j.yrtph.2019.03.005
PMID:30878574
Abstract

INTRODUCTION

Manganese (Mn) is an essential element required for several biological systems. However, it is toxic in excessive accumulation. The toxic effects following Mn overexposure is well known in the CNS but other studies evaluating other target tissues remain scarce.

OBJECTIVE

This study aimed to investigate sex-related differences in oxidative stress, metabolic parameters and Mn deposition in peripheral organs of Wistar rats exposed to subacute model of intoxication.

METHODS

Male and female adult Wistar rats received 6 or 15 mg/kg of MnCl, intraperitoneally, 5 days a week, for 4 consecutive weeks to mimic subacute intoxication. Control group received sterile saline 0,9% following the same protocol. After this period, the metal accumulation, oxidative stress, mitochondrial activity and histological parameters in cardiac muscle, kidney, lungs and liver were analysed.

RESULTS

Increased Mn concentrations were found in all organs, especially kidneys. The cardiac muscle analysis revealed increased lipid peroxidation and decreasing of GSH levels in both doses of Mn in male and female rats. The increase of lipid peroxidation in liver was more evident in the male group, and there was a significant decrease of antioxidant capacity in males' kidney. Nevertheless, there was an increase of mitochondrial complex I activity in kidney of females and increase of mitochondrial complex II activity in male group. Histological analysis revealed morphological changes in hepatic and pulmonary tissue.

CONCLUSION

Taken together, our results showed that subacute Mn exposure lead to significant metabolic, biochemical alterations especially in kidney and liver. Nevertheless, despite Mn deposition was virtually the same in the peripheral organs of male and female rats, it promotes different toxic effects between sexes.

摘要

简介

锰(Mn)是几个生物系统所必需的微量元素。然而,过量积累会导致其毒性。过量暴露于 Mn 后对中枢神经系统的毒性作用是众所周知的,但其他评估其他靶组织的研究仍然很少。

目的

本研究旨在探讨雄性和雌性 Wistar 大鼠在亚急性中毒模型中暴露于 Mn 后外周器官氧化应激、代谢参数和 Mn 沉积的性别差异。

方法

雄性和雌性成年 Wistar 大鼠分别腹腔注射 6 或 15mg/kg 的 MnCl2,每周 5 天,连续 4 周,以模拟亚急性中毒。对照组按相同方案给予无菌生理盐水 0.9%。在这段时间后,分析心肌、肾脏、肺和肝脏中的金属积累、氧化应激、线粒体活性和组织学参数。

结果

所有器官,特别是肾脏,都发现 Mn 浓度增加。心肌分析显示,雄性和雌性大鼠的两种 Mn 剂量均导致脂质过氧化增加和 GSH 水平降低。肝中脂质过氧化的增加在雄性组更为明显,而雄性肾脏的抗氧化能力显著下降。然而,女性肾脏的线粒体复合物 I 活性增加,而男性组的线粒体复合物 II 活性增加。组织学分析显示肝和肺组织的形态变化。

结论

综上所述,我们的结果表明,亚急性 Mn 暴露导致代谢、生化改变显著,尤其是在肾脏和肝脏。然而,尽管 Mn 在雄性和雌性大鼠的外周器官中的沉积几乎相同,但它在性别之间引起了不同的毒性作用。

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