Genotoxicity and mutagenicity evaluation of isoquercitrin-γ-cyclodextrin molecular inclusion complex using Ames test and a combined micronucleus and comet assay in rats

J Toxicol Sci. 2022;47(6):221-235. doi: 10.2131/jts.47.221.

Abstract

Flavonoids such as quercetin and its glucosides, especially isoquercitrin are well known as anti-inflammatory, anti-allergic, and anti-carcinogenic, etc. The safety of isoquercitrin formulations needs to be established prior to their use in functional food applications. The mutagenicity and genotoxicity of the IQC-γCD inclusion complex were assessed with three standard assays of the bacterial reverse mutation assay (Ames test) and using a combined in-vivo micronucleus and comet assay under the Organisation for Economic Co-operation and Development (OECD) guidelines. In combined rat bone marrow micronucleus and rat liver comet assay performed in male Sprague Dawley (SD) rats, the various doses of IQC-γCD inclusion complex (max. 2000 mg/kg bw) and positive controls ethyl methanesulfonate (EMS) and mitomycin C (MMC), respectively, and negative control (vehicle) were administrated. The results of the Salmonella typhimurium mutagenicity assay (strains TA100, TA1535, WP2uvrA, TA98, and TA1537) after exposure to the IQC-γCD inclusion complex with the absence and presence of the metabolic activation system (S9 fraction from rat liver) revealed a weakly positive response but with no biologically relevant mutagenicity at the conditions examined according to recommended regulatory guidelines. The combined micronucleus and comet assay results reveal that the IQC-γCD inclusion complex did not induce in-vivo genotoxic potential or indication of any oxidative DNA damage in rat liver tissues. Altogether, considering the results of the study, it is unlikely that the consumption of IQC-γCD inclusion complex as food or supplement would present any concern for humans regarding the mutagenicity and genotoxicity.

Keywords: Bacterial reverse mutation assay (Ames test); Combined comet/micronucleus assays; Genotoxicity; Isoquercitrin; Mutagenicity; Safety; Toxicity.

MeSH terms

  • Animals
  • Comet Assay
  • DNA Damage
  • Male
  • Micronucleus Tests / methods
  • Mutagenicity Tests / methods
  • Mutagens* / toxicity
  • Quercetin / analogs & derivatives
  • Quercetin / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Cyclodextrins*

Substances

  • Mutagens
  • gamma-Cyclodextrins
  • isoquercitrin
  • Quercetin