抄録
Chromated Copper Arsenate (CCA) has been used worldwide as a wood preservative that can cause adverse impacts on human health. CCA-treated woods are used for many applications such as building construction, playground equipment and flower bed etc. Whereas Cr and As are known to cause respiratory diseases in human, combined effects of these metals have not been elucidated in vivo. Herein, As(V), Cr(VI) or their mixture were intratracheally instilled in male C57BL/6J mice to assess inflammation, cytotoxicity, and cell proliferation on days 2, 7, and 14. We found that the co-treatment with As(V) and Cr(VI) caused pulmonary inflammation, which peaked on day 7, and decreased thereafter, as assessed by bronchoalveolar lavage (BAL). In comparison with each metal treatment on day 2, concurrent As exposure worsened Cr(VI)-induced acute pulmonary inflammation. This finding was supported by the evidence of elevated IL-6 and LDH activity in BAL and enhanced caspase-3/7, -8 and -9 activities, cyclin D1 expression, ROS generation, and GSH and GSSG contents in the lung by co-treatment, when compared with the controls. Investigation of cell signaling demonstrated that ERK, JNK and p38 MAPK were phosphorylated by either Cr(VI) exposure or combined treatment. These findings suggest that acute pulmonary responses were enhanced by co-administering Cr(VI) with As(V), and these effects might be associated with MAPK signaling and oxidative stress.
