Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum.

Abstract

Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. However, the pharmaceutical and toxicological effects of cinnabar, especially in the whole organism, were subjected to few investigations. In this study, an NMR-based metabolomics approach has been applied to investigate the toxicological effects of cinnabar after intragastrical administration (dosed at 0.5, 2 and 5 g/kg body weight) on male Wistar rats. Liver and kidney histopathology examinations and serum clinical chemistry analyses were also performed. The 1H NMR spectra were analyzed using multivariate pattern recognition techniques to show the time- and dose-dependent biochemical variations induced by cinnabar. The metabolic signature of urinalysis from cinnabar-treated animals exhibited an increase in the levels of creatinine, acetate, acetoacetate, taurine, hippurate and phenylacetylglycine, together with a decrease in the levels of trimethyl-N-oxide, dimethylglycine and Kreb's cycle intermediates (citrate, 2-oxoglutarate and succinate). The metabolomics analyses of serum showed elevated concentrations of ketone bodies (3-d-hydroxybutyrate and acetoacetate), branched-chain amino acids (valine, leucine and isoleucine), choline and creatine as well as decreased glucose, lipids and lipoproteins from cinnabar-treated animals. These findings indicated cinnabar induced disturbance in energy metabolism, amino acid metabolism and gut microflora environment as well as slight injury in liver and kidney, which might indirectly result from cinnabar induced oxidative stress. This work illustrated the high reliability of NMR-based metabolomic approach on the study of the biochemical effects induced by traditional Chinese medicine.

• Authors: Lai Wei, Peiqiu Liao, Huifeng Wu, Xiaojing Li, Fengkui Pei, Weisheng Li, Yijie Wu
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 227 Issue 3 Pg. 417-29 (Mar 15 2008) ISSN: 0041-008X [Print] United States
• PMID: 18164359 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mercury Compounds
• cinnabar

Topics

• Animals
• Kidney (drug effects)
• Least-Squares Analysis
• Liver (drug effects)
• Male
• Medicine, Chinese Traditional
• Mercury Compounds (toxicity)
• Nuclear Magnetic Resonance, Biomolecular (methods)
• Rats
• Rats, Wistar
• Serum (chemistry, metabolism)
• Urinalysis
• Urine (chemistry)