Toxic effects of arsenic trioxide on spermatogonia are associated with oxidative stress, mitochondrial dysfunction, autophagy and metabolomic alterations

被引:46
作者
Chen, Hanming [1 ]
Liu, Gaoyang [1 ]
Qiao, Na [1 ]
Kang, Zhenlong [1 ]
Hu, Lianmei [1 ]
Liao, Jianzhao [1 ]
Yang, Fan [1 ]
Pang, Congying [1 ]
Liu, Bingxian [1 ]
Zeng, Qiwen [1 ]
Li, Yao [1 ]
Li, Ying [1 ]
机构
[1] South China Agr Univ, Coll Vet Med, Guangzhou 510642, Peoples R China
基金
美国国家科学基金会;
关键词
Arsenic trioxide; Oxidative stress; Mitochondria dysfunction; Autophagy; Metabolomics analysis; GC-1 spermatogonial cells; GC-1 SPG CELLS; DRINKING-WATER; EXPOSURE; EXPRESSION; SPERMATOGENESIS; PROLIFERATION; INFLAMMATION; PROGRESSION; APOPTOSIS; PROMOTES;
D O I
10.1016/j.ecoenv.2019.110063
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Arsenic is a toxic metalloid that can cause male reproductive malfunctions and is widely distributed in the environment. The aim of this study was to investigate the cytotoxicity of arsenic trioxide (ATO) induced GC-1 spermatogonial (spg) cells. Our results found that ATO increased the levels of catalase (CAT) and malonaldehyde (MDA) and reactive oxygen species (ROS), while decreasing glutathione (GSH) and the total antioxidant capacity (T-AOC). Therefore, ATO triggered oxidative stress in GC-1 spg cells. In addition, ATO also caused severe mitochondria] dysfunction that included an increase in residual oxygen consumption (ROX), and decreased the routine respiration, maximal and ATP-linked respiration (ATP-L-R), as well as spare respiratory capacity (SRC), and respiratory control rate (RCR); ATO also damaged the mitochondrial structure, including mitochondrial cristae disordered and dissolved, mitochondria] vacuolar degeneration. Moreover, degradation of p62, LC3 conversion, increasing the number of acidic vesicle organelles (AVOs) and autophagosomes and autolysosomes are demonstrated that the cytotoxicity of ATO may be associated with autophagy. Meanwhile, the metabolomics analysis results showed that 20 metabolites (10 increased and 10 decreased) were significantly altered with the ATO exposure, suggesting that maybe there are the perturbations in amino acid metabolism, lipid metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins. We concluded that ATO was toxic to GC-1 spg cells via inducing oxidative stress, mitochondria] dysfunction and autophagy as well as the disruption of normal metabolism. This study will aid our understanding of the mechanisms behind ATO-induced spermatogenic toxicity.
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页数:10
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共 69 条
[1]   Oxidative stress and male reproductive health [J].
Aitken, Robert J. ;
Smith, Tegan B. ;
Jobling, Matthew S. ;
Baker, Mark A. ;
De Iuliis, Geoffry N. .
ASIAN JOURNAL OF ANDROLOGY, 2014, 16 (01) :31-38
[2]   Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells [J].
Alarifi, Saud ;
Ali, Daoud ;
Alkahtani, Saad ;
Siddiqui, Maqsood A. ;
Ali, Bahy A. .
ONCOTARGETS AND THERAPY, 2013, 6 :75-84
[3]  
Azad MB, 2009, ANTIOXID REDOX SIGN, V11, P777, DOI [10.1089/ars.2008.2270, 10.1089/ARS.2008.2270]
[4]   Arsenic Exposure in Children through Drinking Water in Different Districts of Sindh, Pakistan [J].
Baig, Jameel Ahmed ;
Kazi, Tasneem Gul ;
Mustafa, Muhammad Ayaz ;
Solangi, Imam Bakhsh ;
Mughal, Mirza Junaid ;
Afridi, Hassan Imran .
BIOLOGICAL TRACE ELEMENT RESEARCH, 2016, 173 (01) :35-46
[5]   Protective effects of quercetin against arsenic-induced testicular damage in rats [J].
Baltaci, B. B. ;
Uygur, R. ;
Caglar, V. ;
Aktas, C. ;
Aydin, M. ;
Ozen, O. A. .
ANDROLOGIA, 2016, 48 (10) :1202-1213
[6]   Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies [J].
Bhatti, Jasvinder Singh ;
Bhatti, Gurjit Kaur ;
Reddy, P. Hemachandra .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2017, 1863 (05) :1066-1077
[7]   Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells [J].
Brown, MR ;
Miller, FJ ;
Li, WG ;
Ellingson, AN ;
Mozena, JD ;
Chatterjee, P ;
Engelhardt, JF ;
Zwacka, RM ;
Oberley, LW ;
Fang, X ;
Spector, AA ;
Weintraub, NL .
CIRCULATION RESEARCH, 1999, 85 (06) :524-533
[8]   Defective Human Sperm Cells Are Associated with Mitochondrial Dysfunction and Oxidant Production [J].
Cassina, Adriana ;
Silveira, Patricia ;
Cantu, Lidia ;
Maria Montes, Jose ;
Radi, Rafael ;
Sapiro, Rossana .
BIOLOGY OF REPRODUCTION, 2015, 93 (05)
[9]  
Chen Wei, 2008, Zhongguo Zhong Yao Za Zhi, V33, P2823
[10]  
Chiarelli Roberto, 2012, Cells, V1, P597, DOI 10.3390/cells1030597