The Research On The Harmful Element Speciation And Safety Of Toxic Mineral-containing Prescriptions

Mineral-containing medicines(MCM)have been used as a type of traditional Chinese medicines(TCMs)and Indian Ayurvedic medicines for thousands of years under the medical theory that using a poison to attack another poison or to fight against malignant diseases.In Chinese Pharmacopoeia,at least 46 prescription contained cinnabaris to treat insomnia,continuous palpitation,and realgar(rabiagar)is also used in western medicine to treat hematologic malignancies.As producing toxicity to the liver,brain,kidney,the reproductive systems and other organs,arsenic and mercury are well-known toxic,which justifiably alarms the public and is of escalating concern.Arsenic is well-known for its toxicity,and the toxicity of realgar-containing TCMs have also been reported,such as realgar-induced renal injury To some extent.In recent years,the toxicity from realgar and cinnabaris containing TCMs have been reported in humans including realgar induced acute renal failure.Herein,mineral-containing TCMs in which the arsenic contents are thousands of folds over the allowable limits in western countries are forbidden in The United States and European market.This situation not only slowed down the internationalization of TCMs,but also restricted medical innovation and development.The total content of harmful elements in vivo and in vitro have been studied to evaluate the toxicity of mineral medicine,but the forms and the valence states have rarely attention.while the form of heavy metals and harmful elements have great correlation with valence and toxicity,arsenic mineral drugs,for example,the main including arsenite(arsenic)realgar,orpiment,arsenic acid,arsenic anhydride,trichloride arsenic,etc.,have only two valence states of which As(Ⅲ)and As(V),while the toxicity is large different.60-fold over As(V),the As(Ⅲ)is the leading cause of acute arsenic poisoning,the toxicity of the organic arsenic which was transformed by the inorganic arsenic after taken is also different.Thus exploring the forms and the valence states of mineral drugs and their drugs preparations accumulated in the body is of great necessity.To date,sample pretreatment,and morphology separation are needed to the finally detect the valence state.In the determination of both to prevent heavy metal and harmful elements in the mutual transformation between different valence state,and to ensure that the valence and form all is separated out.Since the toxicity of different forms of arsenic is not identical,arsenic speciation in tissues should be determined before the explaining the toxicity of realgar-containing TCMs.In this study,a notable example Xiao-Er-Zhi-Bao-Wan(XEZBW),a realgar-containing TCM(3.6% realgar,w/w)which has been widely used to treat infant vomiting,diarrhea and cold,and a prescription medicine,An-Gong-Niu-Huang-Wan was instanced.By using the technology of high-performance liquid chromatography inductively coupled mass spectrometry(HPLC-ICP-MS),different arsenic speciation in liver and kidney of rats were determined.The histopathology and blood biochemistry were further investigated before the elucidation of the relationship between the accumulation of arsenic speciation in vivo and its toxicity.The conclusions was obtained as following,the conversion of realgarn in rats is very low,and realgar metabolism is different from other arsenic compounds.Combined with toxicity studies and arsenic forms metabolism and accumulation in the body,thought to detect the arsenic forms in organs is of great significance.Because the content of total arsenic is 2-fold compared with the blank group,while the accumulation of the DMA is 6 times compared with the blank group,and no accumulation was seen in the other arsenic forms,this may prove that DMA is a major contributor to arsenic poisoning.