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维生素 D 对暴露于代森锰锌(锰/锌乙撑双二硫代氨基甲酸盐)的雄性和雌性成年 Wistar 大鼠行为和氧化参数的神经保护作用。

Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

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) - Ambulatório Médico Universitário, Campus de Joaçaba, Joaçaba, SC, 89600-000, Brazil.

Laboratório de Solos, Universidade Do Oeste de Santa Catarina (UNOESC), Campus de Campos Novos, SC, Brazil.

出版信息

Mol Neurobiol. 2023 Jul;60(7):3724-3740. doi: 10.1007/s12035-023-03298-8. Epub 2023 Mar 20.

DOI:10.1007/s12035-023-03298-8
PMID:36940076
Abstract

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 μg/kg or 25 μg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

摘要

农民工持续暴露于农药下是一个严重的公共卫生问题。代森锰锌(MZ)是一种与激素、行为、遗传和神经退行性变化相关的农药,主要与氧化应激有关。维生素 D 是一种很有前途的分子,可作为对抗大脑衰老的保护剂。本研究旨在评估维生素 D 对暴露于 MZ 的雄性和雌性 Wistar 大鼠的神经保护作用。动物接受腹腔注射 40mg/kg 的 MZ 和灌胃给予 12.5μg/kg 或 25μg/kg 的维生素 D,每周两次,持续 6 周。锰的浓度在两性的海马体和雌性的纹状体中均显著增加,而锌则没有显著增加。MZ 中毒导致脑组织中线粒体发生变化,并引起焦虑样效应,尤其是在雌性中。在中毒大鼠中观察到抗氧化酶的改变,主要是过氧化氢酶活性的改变。总之,我们的结果表明,暴露于 MZ 会导致锰在脑组织中的积累,并且性别之间的行为和代谢/氧化损伤存在差异。此外,维生素 D 的给药可有效预防农药造成的损害。

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本文引用的文献

1
Vitamin D preserves blood retinal barrier integrity in an model of diabetic retinopathy.维生素D在糖尿病性视网膜病变模型中可维持血视网膜屏障的完整性。
Front Pharmacol. 2022 Aug 26;13:971164. doi: 10.3389/fphar.2022.971164. eCollection 2022.
2
Widespread pesticide contamination of drinking water and impact on cancer risk in Brazil.饮用水中广泛存在的农药污染及其对巴西癌症风险的影响。
Environ Int. 2022 Jul;165:107321. doi: 10.1016/j.envint.2022.107321. Epub 2022 Jun 3.
3
Low level of mancozeb exposure affects ovary in mice.低水平代森锰锌暴露会影响小鼠的卵巢。
Ecotoxicol Environ Saf. 2022 Jul 1;239:113670. doi: 10.1016/j.ecoenv.2022.113670. Epub 2022 May 24.
4
Protective Effects of Probucol on Different Brain Cells Exposed to Manganese.普罗布考对暴露于锰的不同脑细胞的保护作用。
Neurotox Res. 2022 Feb;40(1):276-285. doi: 10.1007/s12640-021-00458-3. Epub 2022 Jan 18.
5
1α,25-dihydroxyvitamin D protects retinal ganglion cells in glaucomatous mice.1α,25-二羟维生素 D 可保护青光眼小鼠的视网膜神经节细胞。
J Neuroinflammation. 2021 Sep 16;18(1):206. doi: 10.1186/s12974-021-02263-3.
6
Systemic effects of the pesticide mancozeb - A literature review.代森锰锌的系统作用——文献综述。
Eur Rev Med Pharmacol Sci. 2021 Jun;25(11):4113-4120. doi: 10.26355/eurrev_202106_26054.
7
Intranasal exposure of manganese induces neuroinflammation and disrupts dopamine metabolism in the striatum and hippocampus.鼻腔暴露于锰会引起神经炎症,并破坏纹状体和海马体中的多巴胺代谢。
Neurosci Lett. 2020 Nov 1;738:135344. doi: 10.1016/j.neulet.2020.135344. Epub 2020 Sep 1.
8
MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.微小RNA改变作为癌症和神经退行性疾病的早期生物标志物:农药暴露带来的新挑战
Toxicol Rep. 2020 May 21;7:759-767. doi: 10.1016/j.toxrep.2020.05.003. eCollection 2020.
9
Neuron-Specific Vitamin D Signaling Attenuates Microglia Activation and CNS Autoimmunity.神经元特异性维生素D信号传导可减轻小胶质细胞激活和中枢神经系统自身免疫。
Front Neurol. 2020 Jan 31;11:19. doi: 10.3389/fneur.2020.00019. eCollection 2020.
10
The Role of Sex and Sex Hormones in Neurodegenerative Diseases.性别和性激素在神经退行性疾病中的作用。
Endocr Rev. 2020 Apr 1;41(2):273-319. doi: 10.1210/endrev/bnz005.