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大鼠急性系统性铊中毒产生氧化应激:金属硫蛋白和普鲁士蓝的缓解作用。

The acute systemic toxicity of thallium in rats produces oxidative stress: attenuation by metallothionein and Prussian blue.

机构信息

Laboratorio de Neuroprotección, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos Cuernavaca, Av. Universidad 1001 Col. Chamilpa, Cuernavaca, C.P. 62209, Morelos, Mexico.

Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, Mexico.

出版信息

Biometals. 2021 Dec;34(6):1295-1311. doi: 10.1007/s10534-021-00343-8. Epub 2021 Sep 16.

Abstract

Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental contamination by Tl has been reported in several countries, urging the need for studies to determine the impact of endogenous and exogenous mechanisms preventing thallium toxicity. The cytoprotective effect of metallothionein (MT), a protein with high capacity to chelate metals, at two doses (100 and 600 µg/rat), was tested. Prussian blue (PB) (50 mg/kg) was administered alone or in combination with MT. A dose of Tl (16mg/kg) was injected i.p. to Wistar rats. Antidotes were administered twice daily, starting 24h after Tl injection, for 4 days. Tl concentrations diminished in most organs (p < 0.05) by effect of PB, alone or in combination with MT, whereas MT alone decreased Tl concentrations in testis, spleen, lung and liver. Likewise, brain thallium also diminished (p < 0.05) by effect of PB and MT alone or in combination in most of the regions analyzed (p < 0.05). The greatest diminution of Tl was achieved when the antidotes were combined. Plasma markers of renal damage increased after Tl administration, while PB and MT, either alone or in combination, prevented the raise of those markers. Only MT increased the levels of reduced glutathione (GSH) in the kidney. Finally, increased Nrf2 was observed in liver and kidney, after treatment with MT alone or in combination with PB. Results showed that MT alone or in combination with PB is cytoprotective after thallium exposure.

摘要

铊(TI)是毒性最大的重金属之一。人类通过受污染的饮用水以及通过饮用水进入食物而接触到 Tl,这对健康构成威胁。最近,几个国家都报告了铊的环境污染情况,因此迫切需要研究来确定内源性和外源性机制对铊毒性的影响。在两种剂量(100 和 600 µg/大鼠)下测试了金属硫蛋白(MT)的细胞保护作用,MT 是一种具有高金属螯合能力的蛋白质。单独或与 MT 联合给予普鲁士蓝(PB)(50 mg/kg)。腹腔内注射铊(Tl)(16mg/kg)给 Wistar 大鼠。解毒剂每日两次给药,在 Tl 注射后 24 小时开始,持续 4 天。单独或与 MT 联合使用 PB 可降低大多数器官中的 Tl 浓度(p<0.05),而 MT 单独可降低睾丸、脾脏、肺和肝脏中的 Tl 浓度。同样,大脑中的铊也因 PB 和 MT 单独或联合的作用而减少(p<0.05)在大多数分析的区域(p<0.05)。当解毒剂联合使用时,铊的减少量最大。铊给药后,血浆肾损伤标志物增加,而 PB 和 MT 单独或联合使用可防止这些标志物升高。只有 MT 增加了肾脏中还原型谷胱甘肽(GSH)的水平。最后,在单独或与 PB 联合使用 MT 治疗后,观察到肝脏和肾脏中 Nrf2 增加。结果表明,MT 单独或与 PB 联合使用对铊暴露具有细胞保护作用。

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