Details

Autor(en) / Beteiligte

• Tian, Xiaolin
• Xie, Jiaxin
• Chen, Xushen
• Dong, Nisha
• Feng, Jing
• Gao, Yi
• Tian, Fengjie
• Zhang, Wenping
• Qiu, Yulan
• Niu, Ruiyan
• Ren, Xuefeng
• Yan, Xiaoyan

Titel

Deregulation of autophagy is involved in nephrotoxicity of arsenite and fluoride exposure during gestation to puberty in rat offspring

Ist Teil von

• Archives of toxicology, 2020-03, Vol.94 (3), p.749-760

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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), NaAsO 2 (50 mg/L), or NaF (100 mg/L) with NaAsO 2 (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.