Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 221, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.112442
Keywords
Arsenic; Antimony; Autophagy; Pyroptosis; Nephrotoxicity
Categories
Funding
- National Natural Science Foundation of China [31402264, 31572585]
- Guangzhou Science and Technology Program key projects [201803020003]
- Program of Department of Natural Resources of Guangdong Province [GDME2018C014, GDNRC[2020] 038]
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Arsenic and antimony, commonly found environmental pollutants, can induce histopathological changes and activate autophagy and pyroptosis through oxidative stress, leading to nephrotoxicity.
Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl3) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 mu M), SbCl3 (25 mu M) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/ and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity.
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