氟与砷单独及联合暴露对子代大鼠肾脏毒性损伤与细胞自噬的影响

doi:10.3969/j.issn.1004-616x.2022.03.002

Abstract

Abstract: OBJECTIVE: To evaluate toxicity from chronic fluoride and arsenic exposures to kidneys during pregnancy through adulthood in rats,and to explore the potential regulatory mechanisms. METHODS: Rats were divided into four groups:control (distilled water),fluoride exposure (100 mg/L sodium fluoride),arsenic exposure (75 mg/L sodium arsenate),and fluoride and arsenic combined exposure (100 mg/L sodium fluoride+75 mg/L sodium arsenic) groups.The methods of exposure were as follows:from the first day of pregnancy to the 21st day after birth,offspring rats were exposed to fluoride and arsenic toxicity through maternal uterus and breast milk respectively.After weaning,exposure through free drinking water up to 120 days through the same method of exposure as the parents.The kidney coefficient was calculated after weighing the fresh kidney tissues of the offspring male rats.Pathological changes of glomerulus and tubules were observed by Masson staining and transmission electron microscopy.Expression intensity and distribution of autophagy-related proteins in glomerulus and tubules were determined by immunofluorescence technique. RESULTS: Compared with the control group,the renal organ coefficient of the arsenic exposure group was significantly increased (P<0.01).The degrees of renal fibrosis were aggravated after alone and combined exposure of fluoride and arsenic,and renal fibrosis was the most obvious in the fluoride exposed group.Hyperplasia of mesangial cells and vacuolation of mitochondria in podocytes were found in all exposed group.Typical autophagosomes in podocytes were found in the arsenic exposed group.Compared with the control group,the expression levels of autophagy related proteins Beclin1,LC3 and p62 in renal tissues were significantly increased after alone and combined exposure of fluoride and arsenic (P<0.05).Fluorescence intensity and fluorescence area of autophagy-related proteins of glomerulus and renal tubules were also markedly increased (P<0.01). CONCLUSION: Alone and combined exposures to fluoride and arsenic from pregnancy to adulthood induced toxic damage to glomerulus and tubules in renal tissues.Moreover,autophagy of kidney was associated with increasing expressions of autophagy related proteins Beclin1,LC3 and p62.

Key words: fluoride exposure, arsenic exposure, combined exposure of fluoride and arsenic, kidney injury, autophagy

CLC Number:

R994.6

TIAN Xiaolin, YANG Lingling, ZHAO Qian, CHOU Yulan, SUN Zilong, NIU Ruiyan, YAN Xiaoyan. Effects of fluoride and arsenic alone and combined exposures on nephrotoxicity and autophagy in offspring rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(3): 169-177.

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Effects of fluoride and arsenic alone and combined exposures on nephrotoxicity and autophagy in offspring rats

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