Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
The existence of circadian rhythms in the sensitivity to various drugs has been widely known as Chronopharmacology. Miura et al. investigated the time-dependence of cadmium toxicity using a rodent model and clarified the time-dependent lethality of cadmium (Miura et al., 2012). Based on this, the concept of "Chronotoxicology" has also been highlighted. In general, the mechanism of cadmium cytotoxicity has been shown to be mediated by an increase in reactive oxygen species (ROS). The pathway is similar to sleep induction by accumulation of sleep promoting substances, such as oxidized glutathione (GSSG). Thus, we analyzed the effects of cadmium intake on sleep-wake rhythms in rats by monitoring the effects of 1-100 ppm CdCl2 in drinking water. The results showed that the administration of 100 ppm CdCl2 for 28 hours increased non-REM sleep and decreased locomotion at night (active phase of rats). GSSG level in rat fore brains after 28-h 100 ppm CdCl2 was similar to the level in cultured astrocytes treated with 0.005% hydrogen peroxide. Therefore, it is suggested that cadmium-induced sleep is a consequence of oxidative stress. Since GSSG is an endogenous sleep substance, it is suggested that cadmium may induce sleepiness by occupying an endogenous sleep-inducing mechanism.
