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Fluoride enhances generation of reactive oxygen and nitrogen species, oxidizes hemoglobin, lowers antioxidant power and inhibits transmembrane electron transport in isolated human red blood cells
Ecotoxicology and Environmental Safety ( IF 6.2 ) Pub Date : 2020-11-10 , DOI: 10.1016/j.ecoenv.2020.111611
Nikhil Maheshwari , Neha Qasim , Ruhi Anjum , Riaz Mahmood

Fluoride is a widespread environmental pollutant that at high levels exerts numerous deleterious effects on human health. The toxic effects of fluoride are a matter of serious concern since many countries have regions of endemic fluorosis. The main source of fluoride exposure for humans is intake of contaminated groundwater. Fluoride is absorbed from the gastrointestinal tract and enters the circulating blood, where the abundant red blood cells (RBC) are an early and major target of fluoride toxicity. Chronic fluoride exposure generates free radicals, reactive species which leads to redox imbalance, cytotoxicity and hematological damage. This study aimed to determine the effect of sodium fluoride (NaF) on human RBC under in vitro conditions. Isolated RBC were incubated with different concentrations of NaF (10–500 µM) for 8 h at 37 °C. Several biochemical parameters were determined in hemolysates or whole cells. Treatment of RBC with NaF enhanced the generation of reactive oxygen and nitrogen species. This increased the oxidation of hemoglobin to yield methemoglobin and oxoferrylhemoglobin, which are inactive in oxygen transport. NaF treatment increased the degradation of heme causing release of free iron from its porphyrin ring. Cellular antioxidant power was significantly decreased in NaF-treated RBC, lowering the metal reducing and free radical quenching ability of cells. The two pathways of glucose metabolism in RBC i.e. glycolysis and hexose monophosphate shunt, were inhibited. NaF also inhibited the plasma membrane redox system, and its associated ascorbate free radical reductase, to disrupt transmembrane electron transport. These results suggest that fluoride generates reactive species that cause extensive oxidative modifications in human RBC.



中文翻译:

氟化物增加了活性氧和氮的产生,氧化了血红蛋白,降低了抗氧化能力,并抑制了分离的人红细胞中的跨膜电子转运

氟化物是一种广泛的环境污染物,高浓度时会对人体健康产生许多有害影响。由于许多国家都有地方性氟中毒地区,氟化物的毒性作用引起了人们的严重关注。对人类而言,氟暴露的主要来源是摄入受污染的地下水。氟化物从胃肠道吸收并进入循环血液,在那里丰富的红细胞(RBC)是氟化物毒性的早期和主要靶标。长期接触氟化物会产生自由基和反应性物种,从而导致氧化还原失衡,细胞毒性和血液学损害。这项研究旨在确定氟化钠(NaF)在体外条件下对人RBC的影响。将分离的RBC与不同浓度的NaF(10–500 µM)在37°C下孵育8小时。确定了溶血产物或全细胞中的几个生化参数。用NaF处理RBC增强了活性氧和氮物质的生成。这增加了血红蛋白的氧化,产生了高铁血红蛋白和氧过氧血红蛋白,它们在氧气的运输中没有活性。NaF处理增加了血红素的降解,导致其卟啉环释放出游离铁。在NaF处理的RBC中,细胞的抗氧化能力显着降低,从而降低了金属还原能力和细胞的自由基淬灭能力。RBC中葡萄糖代谢的两个途径即糖酵解和己糖一磷酸分流被抑制。NaF还抑制质膜氧化还原系统及其相关的抗坏血酸自由基还原酶,破坏跨膜电子传输。

更新日期:2020-11-12
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