A review of cinnabar (HgS) and/or realgar (As4S4)-containing traditional medicines.

ETHNOPHARMOCOLOGICAL RELEVANCE: Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries. AIM OF THE REVIEW: This review uses cinnabar (HgS) and realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives. MATERIALS AND METHODS: A literature search on cinnabar and realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed. RESULTS: Both cinnabar and realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired. CONCLUSION: Chemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.

Essentiality, toxicology and chelation therapy of zinc and copper.

Both zinc and copper are essential minerals that are required for various cellular functions. Although these metals are essential, they can be toxic at excess amounts, especially in certain genetic disorders. Zinc and copper homeostasis results from a coordinated regulation by different proteins involved in uptake, excretion and intracellular storage/trafficking of these metals. Apart from zinc transporters (ZnT) families and Cu-ATPase, metallothionein is an important storage protein for zinc and copper. Metallothioneins are intracellular polypeptides with a remarkable ability to bind metallic ions. These proteins bind both essential metals indispensable for the organism and also toxic metals (e.g. cadmium or lead). Metallothioneins play a critical role to maintain zinc and copper homeostasis. In this review, we summarize the toxicity of zinc and copper and the potential treatment for zinc or copper toxicity by zinc- or copper-specific chelators as well as strategy to up-regulate metallothionein.

Zinc supplementation decreases hepatic copper accumulation in LEC rat: a model of Wilson's disease.

The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.