Realgar (90% of AS4S4) and cinnabar (96% of HgS) have been used in traditional Chinese medicines for thousands of years. Both arsenic and mercury are well-known for toxic effects and the safety of realgar-and cinnabar-containing traditional Chinese medicines is of concern. It is considered that any intentional use of known toxic metals in medicine is an unacceptable risk, while an opposing opinion presumes that realgar and cinnabar have clear pharmacological action with tolerable side effects. This review summarized the progress of toxicological study on realgar-and cinnbar-containing traditional Chinese medicines.
Arsenicals ; adverse effects ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Medicine, Chinese Traditional ; adverse effects ; Mercury Compounds ; adverse effects ; Sulfides ; adverse effects

OBJECTIVETo compare sub-acute toxic effects of cinnabar and Wansheng Huafeng Dan with mercury chloride and methyl-mercury.

METHODHealthy SD rats were orally administered with Wansheng Huafeng Dan (0.42 g x kg(-1)), cinnabar (0.15 g x kg(-1)), HgS (0.15 g x kg(-1)), HgCl2 (0.02 g x kg(-1)), MeHg (0.001 g x kg(-1)) and saline for 21 days under observed and their weights were monitored. After the final administration, they were decapitated and their blood, liver, kidney and brain tissues were collected for calculating hepatic and renal indexes and detecting the contents of serum glutamic pyruvic transaminase, urea nitrogen and creatinine and the mercury accumulation in liver, kidney and brain tissues. Besides, relative expressions of liver metallothionein-1 (MT-1) and cytochrome P450 gene subtypes (Cyp1a1, Cyp2b1, Cyp2e1, Cyp3a2, Cyp4a10) mRNA.

RESULTHgCl2 caused obvious weight lose in rats. Mercury contents in liver and kidney were markedly increased by HgCl2 and MeHg, and MeHg markedly increased mercury contents of brain either, but these advent effects were not notable in Wansheng Huafeng Dan and cinnabar groups. However, blood biochemistry and histopathology did not show significant changes in all groups. The expression of rat hepatic MT-1 mRNA was remarkably induced by both HgCl2 and MeHg. The expression of hepatic Cyp3a2 was increased by Wansheng Huafeng Dan and cinnabar, while the expression of Cyp2e1 was inhibited by HgCl2 and MeHg.

CONCLUSIONThe administration of Wansheng Huafeng Dan with equivalent dose for three weeks shows a much low sub-acute toxicity than HgCl2 and MeHg in rats.

Administration, Oral ; Animals ; Brain ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Mercuric Chloride ; toxicity ; Mercury Compounds ; toxicity ; Methylmercury Compounds ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the toxicity of Cinnabar and Cinnabar-containing traditional medicines (Zhusha Anshenwan) comparable to common mercurials.

METHODThe toxicity of methylmercury (MeHg), mercuric chloride (HgCl2), Cinnabar and Zhusha Anshenwan was studied in cultured human liver HL-7702 cells and in mice following acute and subacute exposures.

RESULTThe 50% lethal concentrations (LC50) of MeHg, HgCl2, Cinnabar and Zhusha Anshenwan in human liver HL-7702 cells were 4.4, 9.2, 2460, 4050 mg x L(-1), respectively . Oral cinnabar at a dose of 20 g x kg(-1) (clinical dosage 250 times) did not kill mouse, but no mouse could survive MeHg at a dose of 0.1 g x kg(-1) or HgCl2 at a dose of 0. 15 g x kg(-1). Subacute toxicity experiment indicated that HgCl2 retarded body weight gain with significant accumulation of Hg in the liver and kidney. In comparison, mercury accumulation after Cinnabar and Zhusha Anshenwan was insignificant. No apparent hepatic and renal dysfunctions were evident under the experimental conditions, but the metallothionein-2 mRNA levels were much higher in HgCl2 group than in other groups.

CONCLUSIONCinnabar and Zhusha Anshenwan are much less toxic than MeHg and HgCl2.

Animals ; Female ; Gene Expression ; drug effects ; Kidney ; drug effects ; physiology ; Liver ; drug effects ; physiology ; Male ; Mercuric Chloride ; administration & dosage ; adverse effects ; Mercury Compounds ; administration & dosage ; adverse effects ; Methylmercury Compounds ; administration & dosage ; adverse effects ; Mice ; Mice, Inbred BALB C ; Random Allocation

OBJECTIVE： To study early toxicity of paracetamol （APAP） to drug-induced liver injury in mice based on lipid metabonomics research， and to provide reference for finding potential biological marker. METHODS： Totally 20 mice were randomly divided into normal group and APAP liver injury group， with 10 mice in each group. APAP liver injury group was given intraperitoneal injection of APAP 300 mg/kg to establish acute liver injury model； normal group was given constant volume of normal saline intraperitoneally. 1 h later， the blood of mice was collected to isolate plasma. UPLC-Triple-TOF-MS method was used to detect plasma metabolites and perform metabonomics analysis. PCA， PLS-DA and OPLS-DA analysis distinguished the difference of metabolism profiles between groups. The lipid metabolites were screened and identified according to HMDB， Metlin and LIPID MAPS databases. Meanwhile， the changes of APAP level in plasma of mice were detected. The lipid metabolites with variable influence in the projection （VIP） greater than 1 and P＜0.05 in OPLS-DA analysis were identified as differential metabolites. The correlation between lipid differential metabolites and plasma APAP level was analyzed. RESULTS： PCA， PLS-DA and OPLS-DA results showed that sample points in normal group and APAP liver injury group were located in different areas with good differentiation. Compared with liver injury group and normal group， levels of 5 fatty acid metabolites were significantly increased or decreased； levels of 8 glycerophospholipids were significantly decreased and one sphingolipids was significantly increased. 9-thiastearic acid， tetradecanedioic acid， 9-hydrogen peroxide-10，12-octadecadienoic acid， L-myristoyl carnitine （fatty acid） and scyphostation A （sphingolipids） levels had a significant correlation with APAP level in plasma. CONCLUSIONS： The plasma lipid metabolomics showed abnormal changes 1 hour after acetaminophen exposure. A total of 14 related lipid differential metabolites are found， and 5 of which are significantly correlated with APAP level in plasma.

Objective:To compare positional and volumetric differences between the gross target volumes (GTV) delineated on three-dimensional CT (3D-CT) referencing 18F-FDG PET/CT and the GTV on the deformed image derived from 3D-CT and 18F-FDG PET/CT for primary thoracic esophageal cancer (EC). Methods:Seventy-two patients underwent chemoradiotherapy were enrolled. All the patients sequentially underwent 18F-FDG PET/CT scans for diagnosis and 3D-CT scans for simulation. The GTV 3D was delineated on 3D-CT without referencing 18F-FDG PET/CT. The GTV PET-ref was delineated on 3D-CT referencing 18F-FDG PET/CT. The GTV PET-regwas delineated on the deformed image derived from 3D-CT and 18F-FDG PET/CT by MIM deformable registration software. The differences in position, volume, length, conformity index (CI), and degree of inclusion (DI) of target volumes were compared, respectively. Results:The median volume of GTV 3D, GTV PET-ref, GTV PET-reg were 44.90, 40.36 and 41.15 cm 3, respectively. There was no statistical difference between the volumes of any two targets. The mean lengths of GTV 3D, GTV PET-ref, GTV PET-reg were 8.54, 9.29 and 8.38 cm, respectively. The length of GTV PET-ref was longer than that of GTV 3D ( t=2.134, P<0.05). The median DIs of GTV PET-ref, GTV PET-regin GTV 3D were 0.86, 0.82( Z=-2.741, P<0.05), and that of GTV 3D in GTV PET-ref, GTV PET-reg were 0.87, 0.84 ( Z=-1.429, P<0.05). The median CIs of GTV 3D in GTV PET-ref and GTV PET-reg were 0.72, 0.68 ( Z=2.756, P<0.05), and the difference was significant. The CIs of GTV 3D and GTV PET-ref, GTV 3D and GTV PET-reg, GTV PET-ref and GTV PET-reg had significant negative correlation with the distance of target centers. Conclusions:There was no significant difference between GTV contoured on three-dimensional CT (3D-CT) referencing 18F-FDG PET/CT and the GTV on the deformed image derived from 3D-CT and 18F-FDG PET/CT either in volume size or in spatial position. Therefore, it is recommended that radiation oncologists can refer to the recent diagnostic PET/CT when delineating the gross target volume for primary thoracic esophageal cancer.