Neurotoxicity of mercury sulfide in the vestibular ocular reflex system of guinea pigs

Abstract

A traditional Chinese mineral medicine, cinnabar, naturally occurring mercuric sulfide (HgS), is still occasionally prescribed, but the neurotoxic effects of HgS have not been elucidated. In this paper, an animal model of the purified HgS intoxication was established in guinea pigs in order to study neurotoxicity and pathophysiology of the vestibular ocular reflex system (VOR). Guinea pigs were dosed with HgS by gastric gavage (0.01, 0.1 and 1.0 g/kg per day) for 7 consecutive days. By means of caloric testing coupled with the electronystagmographic (ENG) recording in guinea pigs, we have found that HgS at a dose of 0.1 g/kg induced reversible caloric hypofunction pattern and at a higher dose of 1.0 g/kg induced irreversible hypofunction of caloric test. Monitoring the mercury contents of various tissues (blood, kidney, liver and cerebellum) by continuous flow and cold vapor atomic absorption spectrometry (AAS) revealed that a certain amount of HgS could be absorbed from the gastrointestinal tract and was detectable in these tissues. In addition to the induced dysfunction of VOR system, HgS also caused disturbance of motor performance in guinea pigs. In enzyme assay, Na+/K+-ATPase activity of cerebellum was also significantly inhibited by HgS. Morphological studies showed partial cell loss only in the cerebellar Purkinje cell layer, but not in the granule cell layer, nor in the vestibular labyrinth. All of these findings suggest that cerebellar Purkinje cells are the sensitive target site responsible for HgS-inducing dysfunctions of both VOR system and the motor performance in guinea pigs. Thus, it is concluded that caloric test coupled with ENG recording in VOR system is certainly a sensitive biomarker for monitoring the neurotoxicity of HgS.

1H NMR-Based Metabolomics and Neurotoxicity Study of Cerebrum and Cerebellum in Rats Treated with Cinnabar, a Traditional Chinese Medicine

“…Cinnabar might induce an irreversible injury of the brain at the higher dose of 5 g/kg BW over a 10-day experimental duration. The cerebellum was more sensitive to cinnabar induction than cerebrum, which was consistent with a reported suggestion that cerebellum is one of the vulnerable sites of action of HgS (Chuu et al, 2001).…”

“…HgS could also induce dysfunctions of both vestibule-ocular reflex (VOR) system and the motor performance in guinea pigs (Chuu et al, 2001;Young et al, 2002). Despite these findings, there are few studies reporting the metabolic profiling of neurotoxicity of cinnabar by NMR.…”

“…Although cinnabar is generally thought to be less toxic in vivo because HgS is a highly stable mercury compound and poorly soluble in water (the solubility product constant Ksp of HgS is 10 -52 in water), several studies have suggested that cinnabar or HgS could be absorbed from the gastrointestinal tract and distributed to kidney, liver, and brain after oral administration of cinnabar (Chuu et al, 2001;2007;Huang et al, 2007;Yeoh et al, 1986;Young et al, 2002). Mercury in its various forms (organic and inorganic mercurial compounds) can lead to neurotoxicity (Chang et al, 1977), including blood-brain barrier damage (Albrecht et al, 1994;Zheng et al, 2003), induction of oxidative stress and production of lipid peroxidation (LPO) in the central nervous system (CNS) (Aschner et al, 2007;Lebel et al, 1991), reduction of neuronal RNA and protein synthesis (Mutkus et al, 2006), disturbance of glycolytic pathway in the brain (Paterson et al, 1971), and inhibition of glutamate uptake in astrocytes and stimulation of neuronal cell body injury (Albrecht et al, 1996;Brookes, 1992;Fonfria et al, 2005).…”

Toxic Effects of Potassium Bromate and Thioglycolate on Vestibuloocular Reflex Systems of Guinea Pigs and Humans

“…In our laboratory, we have established the caloric test coupled with ENG recordings for assessing the function of the VOR system of guinea pigs (Young et al, 1991). We have shown that this system is capable of monitoring the toxic effects of mercury sulfide (Chuu et al, 2001). The caloric test was performed after 14 consecutive days of administration.…”

“…The aging effect on the caloric test leads to the significantly decreased SPV, rather than increased SPV (caloric hyperfunction) (Mulch and Petermann, 1979). Since bilateral caloric hyperfunction is caused by either cerebellar disinhibition or psychosomatic disorder (Young and Nomura, 1995), neurotoxicity to the Purkinje cells of the cerebellum could be due to exposure to alcohol (Seilicovich et al, 1985), metals (Chuu et al, 2001), chemicals (Odkvist et al 1983), or drugs (Young and Huang, 2001). Our 10 hairdresser patients reported here all denied of abuse of alcohol, cigarettes, or drugs.…”