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

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

Mahendra P Kapoor  1 , Masamitsu Moriwaki  1 , Derek Timm  2 , Kensuke Satomoto  3 , Kazuyuki Minegawa  4
Affiliations
Free article

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

Mahendra P Kapoor et al. J Toxicol Sci. 2022.
Free article

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.

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