Co-exposure to Arsenic-Fluoride Results in Endoplasmic Reticulum Stress-Induced Apoptosis Through the PERK Signaling Pathway in the Liver of Offspring Rats
Arsenic and fluoride are two of the major groundwater pollutants. To better understand the liver damage induced during development, 24 male rats exposed to fluoride (F), arsenic (As), and their combination (As + F) from the prenatal stage to 90 days after birth were selected for analysis. Histopathological results showed vacuolar degeneration in the As and As + F groups. Compared to those in the control group, aspartate aminotransferase and alanine aminotransferase levels were significantly increased in the combined group. Catalase activity significantly decreased in the treatment groups compared to that in the controls, and the malondialdehyde content in the As and As + F groups was significantly higher than those in the control group. We further evaluated whether this damage is linked to endoplasmic reticulum stress and its related pathways. The mRNA expression levels of PERK, GRP78, EIF2α, ATF4, and CHOP as well as the protein levels of CHOP was significantly increased in the As + F group compared with the control group. These results demonstrate that As, F, and their combination could lead to liver function damage and reduce the antioxidant capacity of the liver to cause oxidative damage to tissues. Moreover, the combination of As and F triggers endoplasmic reticulum stress-induced apoptosis in liver cells by activating the PERK pathway in the unfolded protein response. As and F seem to have different independent effects, whereas their combination resulted in more severe effects overall.
KeywordsFluoride Arsenic Arsenic-fluoride combination Endoplasmic reticulum stress Liver
This research was sponsored by the China National Natural Science Foundation (81872715), the Postdoctoral Science Foundation of China (2016 M600199), the Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi, the Outstanding Youth Science Foundation of Shanxi Province (201701D211008), the Shanxi Scholarship Council of China (2017-058), and the PhD Start-up Fund of Shanxi Medical University (BS03201647). Applied Basic Research Project (Natural Science Foundation Project) in Shanxi Province of China (201801D121312). Soft Science Research Project in Shanxi Province of China (2018041036-2)
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Conflict of Interest
The authors declare that they have no conflict of interest.
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