Role of connexin32 in zinc oxide nanoparticles induced hepatotoxicity

The hepatotoxicity of zinc oxide nanoparticles(ZnO NPs) is of great concern. Connexin32 (Cx32), as a crucial mediator for various kinds of liver injuries, has little investigation on ZnO NPs-induced hepatotoxicity. In the present study, small interfering RNA were performed to specific knockdown of Cx32 in BRL-3A rat liver cells and AML12 mouse liver cells. The observation indicated that the hepatocyte survivals were improved when Cx32 suppressed. The blockage of ROS transmission between neighboring cells as well as attenuated oxidative stress might be responsible for the protection of Cx32 deficiency on hepatocytes. Furthermore, ROS-related signal proteins, such as JNK, Nrf2/HO-1 and Gli1, were found to be downregulated in the absence of Cx32. These findings indicated that Cx32 knockdown could decrease ZnO NPs-induced hepatotoxicity by weakening oxidative stress, where JNK, Nrf2 and hedgehog signaling pathways might be involved.