Neurotoxic Mechanism of Cinnabar and Mercuric Sulfide on the Vestibulo-Ocular Reflex System of Guinea Pigs

Abstract

Cinnabar, a naturally occurring mercuric sulfide (HgS), has been combined with Chinese herbal medicine as a sedative for more than 2000 years. To date, its neurotoxic effect on the vestibulo-ocular reflex (VOR) system has not been reported. By means of a caloric test coupled with electronystagmographic recordings, the effect of commercial HgS and cinnabar on the VOR system of guinea pigs was studied. HgS or cinnabar was administered orally (1.0 g/kg) to Hartley-strain guinea pigs once daily for 7 consecutive days. A battery of electrophysiological, biochemical, and histopathological examinations were performed. The results showed that HgS induced a 60% caloric response abnormality (40% caloric hyperfunction and 20% hypofunction), whereas the abnormal responses appeared to be more severe (six out of six) in the cinnabar group. The Hg contents of whole blood and cerebellum were increased and correlated to their neurotoxic effects on the VOR system, indicating that both insoluble HgS and cinnabar could be absorbed from the gastrointestinal tract and distributed to the cerebellum. Although the vestibular labyrinth revealed no remarkable change under light microscopy, loss of Purkinje cells in the cerebellum was detected, and the enzymatic Na(+)/K(+)-ATPase activity of cerebellum (a higher inhibitory center of the VOR system) was significantly inhibited by HgS and cinnabar. Moreover, cerebellar nitric oxide (NO) production was increased significantly. Hence, we tentatively conclude that the increased Hg contents in the cerebellum following oral administration of HgS and cinnabar were responsible, at least in part, for the detrimental neurotoxic effect on the VOR system. Potentially, decreasing Na(+)/K(+)-ATPase activity and increasing NO production within the cerebellar regulatory center are postulated to mediate this VOR dysfunction caused by the mercurial compounds and cinnabar.

Mercury in Traditional Medicines: Is Cinnabar Toxicologically Similar to Common Mercurials?

“…In comparison, the ototoxicity produced by methyl mercury was so dramatic and irreversible, even at doses 1/1000 to 1/5000 of cinnabar (24)(25)(26)(27)(28)(29). It should also be pointed out that the dose of cinnabar or mercury sulfide (1.0 g/kg) used in these studies is at least 100-500 times higher than human daily dose (i.e., 50 g/50 kg person, while allowable daily human oral dose is 0.1 -0.5 g) (1).…”

“…In comparison to methyl mercury, oral cinnabar or mercury sulfide administration results in at least 1000-fold less tissue mercury accumulation in mice (24)(25)(26)(27), and in rats (28). Synthetic mercury sulfide was reported to have better bioavailability than cinnabar in mice (18,21), but in other studies, synthetic mercury sulfide was reported to have less oral bioavailability than cinnabar in mice (27) and in guinea pigs (29). This discrepancy could be due to differences in cinnabar processing methods, as well as to animal species or strain variation.…”

Is mercury in Tibetan Medicine toxic? Clinical, neurocognitive and biochemical results of an initial cross-sectional study

“…57 Taken orally HgS can be toxic; high doses in rodents (1.0 g/kg) have been associated with hearing loss, memory, and behavioral problems with long-term administration causing gastrointestinal symptoms, renal dysfunction, and blurred vision. [58][59][60] While not considered to cross the blood-brain barrier or placenta, a small portion of HgS can be reduced in the tissues and exhaled as Hg vapor with accumulation in the cerebral cortex and cerebellum. 56,61 In the current study, Hg in TM was taken at doses far below those associated with HgS toxicity, while Hg in blood and urine (the latter detected in only 20% of patients) were well below international safety levels.…”

Development and Validation of a HPLC-UV Method with Pre-column Derivatization for Determination of Cinnabar in Jufang Zhibao Pills

“…The shocked world of Minamata disease was caused by mercury poisoning in Japan in 1956. It is universally acknowledge that mercury and its compounds exhibit highly chronic toxicity [3] , which has threaten to our kidneys, the central nervous system and the reproductive system [4][5][6][7][8][9][10]. Hence, mercury was strictly limited applied to medicine in international society, which not only affect the medicine export but also damage to the reputation of traditional Chinese medicine.…”