Neurotoxicological effects of cinnabar (a Chinese mineral medicine, HgS) in mice.
Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in combination with traditional Chinese medicine as a sedative for more than 2000 years. Up to date, its pharmacological and toxicological effects are still unclear, especially in clinical low-dose and long-term use. In this study, we attempted to elucidate the effects of cinnabar on the time course of changes in locomotor activities, pentobarbital-induced sleeping time, motor equilibrium performance and neurobiochemical activities in mice during 3- to 11-week administration at a clinical dose of 10 mg/kg/day. The results showed that cinnabar was significantly absorbed by gastrointestinal (G-I) tract and transported to brain tissues. The spontaneous locomotor activities of male mice but not female mice were preferentially suppressed. Moreover, frequencies of jump and stereotype-1 episodes were progressively decreased after 3-week oral administration in male and female mice. Pentobarbital-induced sleeping time was prolonged and the retention time on a rotating rod (60 rpm) was reduced after treatment with cinnabar for 6 weeks and then progressively to a greater extent until the 11-week experiment. In addition, the biochemical changes in blood and brain tissues were studied; the inhibition of Na(+)/K(+)-ATPase activities, increased production of lipid peroxidation (LPO) and nitric oxide (NO) were found with a greater extent in male mice than those in female mice, which were apparently correlated with their differences in the neurological responses observed. In conclusion, these findings, for the first time, provide evidence of the pharmacological and toxicological basis for understanding the sedative and neurotoxic effects of cinnabar used as a Chinese mineral medicine for more than 2000 years.
Huang
Chun-Fa
CF
Institute of Toxicology, National Taiwan University, Taipei 100, Taiwan.
Liu
Shing-Hwa
SH
Lin-Shiau
Shoei-Yn
SY
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017669:Mercury Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D010424:Pentobarbital; D004856:Postural Balance / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012737:Sex Factors; D012890:Sleep / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D004365:Drugs, Chinese Herbal; D017669:Mercury Compounds; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000254:Sodium-Potassium-Exchanging ATPase; D010424:Pentobarbital; C034211:cinnabar