Zinc prevents Cadmium-induced glial stress and activation

The air pollution is known to have serious health effects. However, even if a decrease of air pollutant emissions is carrying on, the risk of morbidity and mortality is increasing. Among the environmental pollutants, the heavy metal cadmium (Cd) has a pivotal role as it is present in pesticides, plastics, smoke cigarette, colors and many other sources. Due to its long half-life, ranging between 15 and 20 years, Cd toxicity has many health effects affecting different organs, including the central nervous system (CNS). As recently reported, Cd is able to affect the blood-brain barrier tight junction integrity thus leading to its impairment. Once inside the CNS, Cd can interact with other cell types belonging to the neurovascular unit (NVU). Among all the cells that constitute the NVU architecture, astrocytes and microglia, through their relationship, have a pivotal role in detecting the needs of neuronal supply and triggering necessary responses for such demands. The toxicity of this metal seems mainly due to a Cd-dependent increase in oxidative stress. On the other hand, it has been reported that zinc (Zn) can counteract this toxic effect, by both competing for the same pathways and preventing the Cd-induced oxidative stress. The aim of this study was to evaluate the role of Zn in ameliorating the Cd toxic effects on astrocyte and microglial cell cultures. The DITNC1 (astrocyte) and BV-2 (microglial cells) cell lines were used in their appropriate growth medium. The stimuli used were cadmium chloride (CdCl2) and zinc chloride (ZnCl2) both at 1 µM concentration for different time of exposure (4-48h). Cell viability assay, immunofluorescent staining and western blotting analyses were performed in order to evaluate the Zn protection against Cd-induced toxicity. Our results demonstrated that Zn is able to counteract the reactive oxygen species (ROS) overproduction during Cd treatment along with a decrease in GRP78 protein expression levels, a well-known ER stress marker. Also, Zn is able to prevent cytochrome C spillage from mitochondria caused by the Cd treatment Most importantly, the presence of Zn counteracts the Cd-dependent increase of glial activation markers, such as GFAP and S100β for astrocytes, and Iba1 and CD86 for microglial cells. Overall, these data demonstrated the protective role of Zn against Cd toxic effects by mitigating both oxidative and ER stress.