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Evaluation of toxic effects induced by arsenic trioxide or/and antimony on autophagy and apoptosis in testis of adult mice

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Abstract

Arsenic trioxide (ATO) and antimony (Sb) are well-known ubiquitous environmental contaminants and cause unpromising male reproductive effects in target and non-target exposed organisms. The main objective of this study was to investigate the effects of ATO or/and Sb on process of autophagy, apoptosis, and reproductive organ in adult mice. For this reason, a total of 32 adult mice were randomly divided into different groups like control group, ATO-treated group, Sb-treated group, and combined group. The duration of current experimental trial was 2 months. Various adverse effects of ATO or/and Sb on sperm parameters, oxidative stress, autophagy, and apoptosis were determined in testis of mice. Results indicated that parameters of sperm quality for organ coefficient, sperm count, ratio of sperm survival, testosterone level, and germ cells were significantly decreased, while malformation rate and vacuolization significantly increased in mice exposed to different treatments. Furthermore, the status of antioxidant index of T-AOC, SOD, and MsrB1 levels was reduced, while MDA increased significantly in ATO + Sb group. Results on TEM investigation determined that the autophagosomes, autolysosome, nuclear pyknosis, and chromatin condensation were prominent ailments, and the levels of autophagy and pro-apoptosis indictors including Beclin1, Atg-5, LC3B/LC3A, caspase-8, cytc, cleaved caspase-3, p53, and Bax were up-regulated in treated group, while the content of an anti-apoptosis maker (Bcl-2) was down-regulated. In conclusion, the results of our experiment suggested that abnormal process of autophagy and apoptosis was triggered by arsenic and antimony, and intensity of toxic effects increased in combined treatments of ATO and Sb.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ATO:

arsenic trioxide

Sb:

antimony

MsrA:

methionine sulfoxide reductase A

MsrB1:

methionine sulfoxide reductase B1

T-AOC:

total antioxidant capacity:

SOD:

superoxide dismutase

MDA:

malondialdehyde

ROS:

reactive oxygen species

Beclin1:

Bcl-2 homologous domain protein

Atg5:

autophagy-related gene 5

LC3:

the microtubule-associated protein 1 light chain 3

Cytc:

cytochrome c:

PBS:

phosphate buffer saline

TBST:

tris buffered saline Tween

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Acknowledgements

The authors would like to kindly thank Sigma, Leica, and Vazyme for their excellent experimental support to this study.

Funding

This work was supported by the National Natural Science Foundation of China (31402264, 31572585) and Guangzhou Planned Program in Science and Technology (NO. 201803020003).

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Authors

Contributions

Conceptualization: Shaofeng Wu, Gaolong Zhong, and Fang Wan

Methodology: Shaofeng Wu, Gaolong Zhong, Xuanxuan Jiang, and Ting Hu

Formal analysis and investigation: Shaofeng Wu, Rao Gan, Juan Lan, and Riming Huang

Writing - original draft preparation: Shaofeng Wu and Lixuan Tang

Writing - review and editing: Lianmei Hu, Hui Zhang, Riaz Hussain, and Riming Huang

Funding acquisition: Zhaoxin Tang and Lianmei Hu

Resources: Lianmei Hu

Supervision: Lianmei Hu

Corresponding author

Correspondence to Lianmei Hu.

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Responsible Editor: Mohamed M. Abdel-Daim

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Highlights

• Arsenic and antimony affect spermatogenesis and testicular morphologic structure.

• They produce oxidative stress, which induce autophagy and apoptosis in the testis.

• Antimony inhibited the autophagy flux in mouse testis.

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Wu, S., Zhong, G., Wan, F. et al. Evaluation of toxic effects induced by arsenic trioxide or/and antimony on autophagy and apoptosis in testis of adult mice. Environ Sci Pollut Res 28, 54647–54660 (2021). https://doi.org/10.1007/s11356-021-14486-1

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