Exposure to fluoride (F) or arsenite (As) through contaminated drinking water has been associated with chronic nephrotoxicity in humans. Autophagy is a regulated mechanism ubiquitous for the body in a toxic environment with F and As, but the underlying mechanisms of autophagy in the single or combined nephrotoxicity of F and As are unclear. In the present study, we established a rat model of prenatal and postnatal exposure to F and As with the aim of investigating the mechanism underlying nephrotoxicity of these pollutants in offspring. Rats were randomly divided into four groups that received NaF (100 mg/L), NaAsO2 (50 mg/L), or NaF (100 mg/L) with NaAsO2 (50 mg/L) in drinking water or clean water during pregnancy and lactation; after weaning, pups were exposed to the same treatment as their mothers until puberty. The results revealed that F and As exposure (alone or combined) led to significant increases of arsenic and fluoride levels in blood and bone, respectively. In this context, F and/or As disrupted histopathology and ultrastructure in the kidney, and also altered creatinine (CRE), urea nitrogen (BUN) and uric acid (UA) levels. Intriguingly, F and/or As uptake induced the formation of autophagosomes in kidney tissue and resulted in the upregulation of genes encoding autophagy-related proteins. Collectively, these results suggest that nephrotoxicity of F and As for offspring exposed to the pollutants from in utero to puberty is associated with deregulation of autophagy and there is an antagonism between F and As in the toxicity autophagy process.

中文翻译：

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自噬的失调与砷的肾毒性和妊娠期至大鼠后代的氟化物暴露有关。

通过受污染的饮用水暴露于氟化物（F）或亚砷酸盐（As）与人类慢性肾毒性有关。自噬是在具有F和As的毒性环境中对人体普遍存在的调节机制，但尚不清楚F和As的单次或联合肾毒性中潜在的自噬机制。在本研究中，我们建立了一个大鼠产前和产后暴露于F和As的大鼠模型，目的是研究这些污染物对后代的肾毒性的潜在机制。大鼠随机分为四组，分别在怀孕期间和饮水或清水中分别接受NaF（100 mg / L），NaAsO2（50 mg / L）或NaF（100 mg / L）和NaAsO2（50 mg / L）的饮用水。哺乳期 断奶后，幼犬要接受与母亲相同的治疗，直到青春期。结果表明，F和As暴露（单独或联合）分别导致血液和骨骼中砷和氟化物含量显着增加。在这种情况下，F和/或As破坏了肾脏的组织病理学和超微结构，还改变了肌酐（CRE），尿素氮（BUN）和尿酸（UA）的水平。有趣的是，F和/或As的摄取会诱导肾脏组织中自噬体的形成，并导致编码自噬相关蛋白的基因上调。总的来说，这些结果表明F和As对于从子宫内到青春期暴露于污染物的后代的肾毒性与自噬的失调有关，并且在毒性自噬过程中F和As之间存在拮抗作用。