Effects of sodium fluoride on MAPKs signaling pathway in the gills of a freshwater teleost, Cyprinus carpio

Exposure to elevated levels of fluoride can cause a variety of adverse effects in fish. Previously we showed that fluoride causes injuries and apoptosis in the gills of Cyprinus carpio. In this study, the effects of fluoride on caspase-3 activity and on accumulation of proteins in the MAPKs pathways were evaluated using Western blotting and immunohistochemistry methods in vivo and in vitro. In vivo experiments showed that the caspase-3 activity increased with fluoride exposure level in a dose-dependent pattern Western blotting and immunohistochemistry results indicated that ERK relative activation tended to decrease as a function of fluoride exposure concentration. In contrast, relative activation of JNK increased with fluoride exposure level. Fluoride exposure did not appear to affect p38 activation. Furthermore, pretreatment of branchial cells with MAPK-specific inhibitors effectively prevented JNK induction and ERK inhibition, respectively, as well as reversed caspase-3 activity in fluoride-treated branchial cells. Our results indicate that activation of JNK and inactivation of ERK were caused by increased ROS and decreased antioxidant capacity in the gills of chronically exposed C. carpio described previously, which eventually caused the observed apoptosis in the fluoride-exposed gills and cells in C. carpio. JNK activation and ERK inactivation mechanism play a crucial role in gill impairment induced by chronic fluorosis. These findings contribute to a better understanding of the initial molecular and cellular events in the gill of fish chronically exposed to fluoride.