title: Anthocyanins suppress the cleavable complex formation by irinotecan and diminish its DNA-strand-breaking activity in the colon of Wistar rats.
abstract: In the present study, the question was addressed whether anthocyanins interfere with the topoisomerase I poison irinotecan in vivo. In vivo complexes of enzyme to DNA bioassay was used to detect irinotecan-induced stabilization of topoisomerase I/DNA complexes and single cell gel electrophoresis to determine DNA-strand-break induction in the colon of male Wistar rats. Furthermore, analysis of anthocyanin concentrations in rat plasma and rat colon was included in the testing, demonstrating that anthocyanins reach the colon and the concentrations do not differ between rats that only received anthocyanins and the anthocyanin/irinotecan group. Blackberry extract was found to significantly reduce irinotecan-mediated topoisomerase I/DNA cleavable complex formation. Overall, anthocyanins did not notably increase cleavable complex formation. However, a significant increase of DNA damage was shown after a single dose of irinotecan as well as the single compounds cyanidin (cy) and cyanidin-3-glucoside (cy-3-g). Furthermore, a significant reduction of irinotecan-induced DNA-strand breaks after a pretreatment with cy, cy-3-g and blackberry extract was observed. Thus, the question arises whether anthocyanin-rich preparations might interfere with chemotherapy or whether, due to low systemic bioavailability, the preparations might provide protective potential in the gastrointestinal tract.
authors.affiliation: Department of Chemistry, Section of Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Esselen
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Barth
authors.forename: Swantje
authors.initials: S
authors.lastname: Winkler
authors.forename: Simone
authors.initials: S
authors.lastname: Baechler
authors.forename: Karlis
authors.initials: K
authors.lastname: Briviba
authors.forename: Bernhard
authors.initials: B
authors.lastname: Watzl
authors.forename: Susanne
authors.initials: S
authors.lastname: Skrbek
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053960:DNA Breaks / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005638:Fruit; D005960:Glucosides / Q000494:pharmacology; D000077146:Irinotecan; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D010936:Plant Extracts; C462279:cyanidin-3-O-beta-glucopyranoside; D000077146:Irinotecan; C017154:cyanidin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin