Cinnabar, a naturally occurring
mercuric sulfide (HgS), has long been used in Chinese
mineral medicine for more than 2000 years; currently it is still used as a
sedative for infants in Asian countries. Since methylmercury is potently ototoxic, whether
cinnabar also induces
hearing impairment is awaited for delineation. In this study, we attempted to explore the toxic effects of
cinnabar on the auditory brainstem response (ABR) system during 2-10 weeks administration at a clinical oral dosage of 10mg/kg/day in mice. The results showed that Hg contents of the brainstem were significantly increased accompanied with gradually progressive abnormality of ABR during 4-10 weeks of
cinnabar administration. The progressive increase in hearing thresholds, prolonged absolute and interwave latencies of ABR apparently exhibited a gender difference. Male mice were more sensitive to
cinnabar in producing
hearing impairment correlated with the biochemical alterations in plasma and brainstem, e.g. an increase of lipid peroxidation (LPO), altered Na(+)/K(+)-
ATPase activities and decrease of
nitric oxide (NO(x)) levels. Moreover, accumulation of Hg contents in brainstem with a greater extent was found in male mice. These findings provide important information that the clinical dosage of
cinnabar (10mg/kg/day) still exhibited
ototoxicity after continuously long-term exposure. The signaling pathway of oxidative stress/Na(+)-K(+)-
ATPase activities/NO of brainstem (a central auditory regulatory system) probably plays an important role in the toxic mechanisms of
cinnabar-induced
ototoxicity. The gender difference in
cinnabar-induced neurotoxic effects merits further investigation.