In vivo genotoxicity of Ginkgo biloba extract in gpt delta mice and constitutive androstane receptor knockout mice.

Abstract

The National Toxicology Program study of Ginkgo biloba extract (GBE), a herbal supplement, reported concerns regarding genotoxicity and clear evidence of hepatocarcinogenicity and liver hypertrophy in mice. To clarify the genotoxicity of GBE in vivo, we performed reporter gene mutation assay using gpt delta mice. We also used a combined liver comet assay and bone marrow micronucleus assay using C3H-derived constitutive androstane receptor knockout (CARKO) and wild-type mice. No remarkable increases in gpt or Spi(-) mutation frequencies were observed in DNA extracted from the livers of gpt delta mice that had been exposed to GBE up to 2000 mg/kg bw/day. In the comet and micronucleus assays, no statistically significant increases in positive cells were observed at doses up to 2000 mg/kg bw/day of GBE in either mouse genotype. The present study provides clear evidence that GBE is not genotoxic in vivo. Our results indicate that GBE-induced hepatocarcinogenesis in mice occurs through a non-genotoxic mode of action.

• Authors: Jun Maeda, Aki Kijima, Kaoru Inoue, Yuji Ishii, Ryohei Ichimura, Shinji Takasu, Ken Kuroda, Kohei Matsushita, Yukio Kodama, Naoaki Saito, Takashi Umemura, Midori Yoshida
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 140 Issue 2 Pg. 298-306 (Aug 01 2014) ISSN: 1096-0929 [Electronic] United States
• PMID: 24824808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Constitutive Androstane Receptor
• Mutagens
• Plant Extracts
• Receptors, Cytoplasmic and Nuclear
• Transferases (Other Substituted Phosphate Groups)
• UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase

Topics

• Animals
• Body Weight (drug effects)
• Comet Assay
• Constitutive Androstane Receptor
• Female
• Ginkgo biloba (chemistry)
• Liver (drug effects)
• Male
• Mice
• Mice, Knockout
• Micronucleus Tests
• Mutagens (toxicity)
• Organ Size (drug effects)
• Plant Extracts (toxicity)
• Receptors, Cytoplasmic and Nuclear (genetics)
• Transferases (Other Substituted Phosphate Groups) (genetics)