Abstract

Highlights

• The exposure of fluoride and arsenic in the mother rats induced the autophagy in the kidney of the offspring mice.
• Under the experimental conditions, the combination of As and F showed certain antagonistic effects.
• The expression of autophagy negative regulator p62 is increased, which may be due to autophagic flow block.

Both arsenic (As) and fluorine (F) are toxic substances widely found in the environment, which threaten to various organs of both human and animals, especially the kidney. In this study, to investigate the individual and combined effects of arsenic (15 mg/L As₂O₃(III)) and fluoride (100 mg/L NaF), arsenic (15 mg/L As₂O₃(III)) and fluoride-arsenic (15 mg/L As₂O₃(III)+100 mg/L NaF) on the renal autophagy during early life, a mouse model of gestationally exposed to As and/or F was established. The results showed that the mRNA expression levels of LC3, LC3I, LC3II, Beclin-1, ULK1, Atg13 and Atg14 were significantly increased with a concomitant decrease in mTOR and Bcl-2 up on individual exposure to As and F rather than in combined (As + F) exposure. In addition, the protein expression levels of LC3-II/LC3-I, Beclin-1, and LAMP1 were significantly increased with a concomitant decrease in mTOR and Bcl-2 in the mice subjected to individual exposure than the combined exposure. Based on the results, it was observed that renal tissue of mice was highly sensitive to F than As. Moreover, the toxicity of the combined (As + F) exposure was significantly lower than that of the individual exposure, which could be attributed due to the antagonism between As and F.

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