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Arsenic and sulfur dioxide co-exposure induce renal injury via activation of the NF-κB and caspase signaling pathway

Author:
Ji, Peng-yu, Li, Zhuo-yu, Wang, Hong, Dong, Jin-tang, Li, Xiu-juan, Yi, Hui-lan
Source:
Chemosphere 2019 v.224 pp. 280-288
ISSN:
0045-6535
Subject:
apoptosis, arsenic, caspases, coal, cytotoxicity, genes, glomerulonephritis, human diseases, kidneys, mice, oxidative stress, signal transduction, sulfur dioxide, transcription factor NF-kappa B
Abstract:
Although emerging evidence suggests positive association of arsenic (As) or sulfur dioxide (SO2) exposure with human diseases, reports concerning the effects of co-exposure of As and SO2 are lacking. Moreover, there is insufficient information in the literature about As and SO2 co-exposure to renal injury. In this study, we focus on the environmental problems of excessive As and SO2 that co-exist in many coal consumption areas. We used both C57BL/6 mice and 293T cells to detect toxicities of As and SO2 exposure alone or in combination. Our results showed that co-exposure significantly increased the hazard compared with exposure to As or SO2 alone. Mouse kidney tissue slices showed that co-exposure caused more severe diffuse sclerosing glomerulonephritis than As and SO2 exposure alone. Meanwhile experiments showed that apoptosis was aggravated by co-exposure of As and SO2 in 293T cells. Because As and SO2 cause cell toxicity through increasing oxidative stress, next we detected ROS and other oxidative stress parameters, and the results showed oxidative stress was increased by co-exposure compared with the other three groups. The expression levels of downstream genes in the NF-κB and caspase pathways were higher in the co-exposure group than in the groups of As or SO2 exposure alone in mice and 293T cells. Based on the above results, co-exposure could induce higher toxicity in vitro and in vivo compared with single exposure to As or SO2, indicating that people living in places that contaminated by As and SO2 may have higher chance to get renal injury.
Agid:
6328980