Realgar, cinnabar and An-Gong-Niu-Huang Wan are much less chronically nephrotoxic than common arsenicals and mercurials

Author:

Lu Yuan-Fu12,Wu Qin1,Yan Jun-Wen1,Shi Jing-Zhen3,Liu Jie14,Shi Jing-Shan12

Affiliation:

1. Department of Pharmacology and Key Lab of Basic Pharmacology of Guizhou, Zunyi Medical College, Zunyi 563003

2. Shanghai University of Traditional Chinese Medicine, Shanghai 20071

3. Guiyang Traditional Medical College, Guiyang 550000, China

4. University of Kansas Medical Center, Kansas City, KS 66160, USA

Abstract

Realgar (As4S4) and cinnabar (HgS) are frequently included in traditional Chinese medicines and Indian Ayurvedic medicines. Both As and Hg are well known for toxic effects, and their safety is of concern. The aim of this study was to compare chronic nephrotoxicity of An-Gong-Niu-Huang Wan (AGNH), realgar and cinnabar with common arsenicals and mercurials. Mice were orally administrated with AGNH (3 g/kg, 6-fold of clinical dose), cinnabar (0.3 g/kg, amount in AGNH) and realgar (0.3 g/kg, amount in AGNH), HgCl2 (0.118 mmol/kg, 1/10 of cinnabar), MeHg (0.012 mmol/kg, 1/100 of cinnabar), NaAsO2 (As3+ 0.028 mmol/kg, 1/100 of realgar) or Na2HAsO4 (As5+ 0.056 mmol/kg, 1/50 of realgar), daily for six weeks, and nephrotoxicity was examined. Animal body weights were decreased by MeHg and HgCl2. Blood urea nitrogen and creatinine levels were elevated by MeHg. Renal pathology was severe in the MeHg and HgCl2 groups, moderate in the arsenite, arsenate and realgar groups and mild in the cinnabar and AGNH groups. Renal Hg accumulation in the MeHg and HgCl2 groups was 50–200 folds higher than the cinnabar group. Expressions of metallothionein-1 and heme oxygenase-1, biomarkers for metal toxicity, were increased 2–5 folds by arsenite, arsenate, MeHg and HgCl2, but not by realgar, cinnabar and AGNH. The chemokine and glutathione- S transferase- α4, markers for inflammation, were also increased by MeHg and HgCl2. Expressions of cell adhesion gene S100a9 and E-cadherin were altered by HgCl2, arsenite and realgar. Taken together, chemical forms of mercury and arsenic are major determinants in their disposition and toxicity.

Publisher

SAGE Publications

Subject

General Biochemistry, Genetics and Molecular Biology

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