Splenocyte apoptotic pathway in mice following oral exposure to cerium trichloride

With their widespread application in agriculture, industry, culture, medicine, and daily life, lanthanide compounds are being brought into the ecological environment and human body through food chains. It is important to know the acute and chronic effects of lanthanides on the environment, nature balance, and the human body after their entry into bodies and the environment. Lanthanides have been demonstrated to cause spleen apoptosis and decreased immunity of mice, but very little is known about the molecular aspects of these mechanism. In order to understand the spleen apoptotic mechanism induced by intragastric administration of 2, 10 and 20 mg kg−1 body weight CeCl3 for consecutive 60 d, we investigated the cerium accumulation, apoptosis, the expression levels of the apoptosis-related cytokines into apoptosis-related genes and proteins. The results demonstrated that cerium had obvious accumulation in the mouse spleen, leading to the significant increase of the spleen indices and splenocyte apoptosis. Furthermore, CeCl3 could effectively activate caspase-3 and -9, decrease the Bcl-2 the levels of gene and protein, and increase the levels of Bax, and cytochrome c genes and their protein expressions, and promote reactive oxygen species production. It implied CeCl3-induced apoptosis in the mouse spleen via intrinsic pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers.

Research highlights
► Exposure to CeCl3 induced splenocyte apoptosis in mice.
► Exposure to CeCl3 promoted the expression of caspase-3, caspase-9 in the spleen.
► Exposure to CeCl3 caused ROS overproduction in the spleen.
► CeCl3-induced apoptosis in splenocyte was primarily via intrinsic pathways.