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• W2324067071 abstract "Event Abstract Back to Event Differences in chemical structure result in opposite cytogenetic behavior of benzodiazepines Maria T. Ekonomopoulou1*, Maria Argyraki1, Doxakis Anestakis1 and Zafiroula Iakovidou-Kritsi1 1 Aristotle University of Thessaloniki, Laboratory of General Biology and Genetics, Greece Introduction. Benzodiazepines (BDZs) belong to the most commonly prescribed drugs for the treatment of a variety of psychological and physical diseases. Especially some of 1,4-BDZs possess a leading role as anxiolytic, sedative, hypnotic, anticonvulsant and muscle relaxant drugs. 1,4-BDZs have an aromatic benzene ring fused to 1,4-diazepine ring with various substituents. Despite their extended use in therapy, they present widely varying pharmacokinetic behavior and the majority of them do not have retrievable genotoxicity or carcinogenicity data. 1,5-BDZs is a group of polycyclic compounds with characteristic seven-membered heterocyclic rings. Though some members of them have important biological properties, there is lack of information on their effect on DNA. Materials and methods. We studied the cytogenetic effects of four of the most widely used 1,4-BDZs, alprazolam (AZ), bromazepam (BZ), diazepam (DZ) and lorazepam (LZ) in normal human lymphocyte cultures, using an expanded sample set, administering them at final concentrations equivalent to oral dosage. Then, we synthesized four 1,5-BDZs with small structural differences and investigated their cytogenetic activity in normal human lymphocyte cultures at concentrations equivalent to the per os doses of the 1,4-BDZs. Sister chromatid exchanges (SCEs) have been used as one of the most sensitive index of cytotoxic activity reflecting instability of DNA or/and a deficiency in DNA repair mechanisms. Proliferation rate index (PRI) has been estimated as a valuable marker of cytostaticity. Results. All four 1,4-BDZs caused a concentration-dependent, statistically significant increase of SCE frequency (p<0.001) followed by a statistically significant decrease of PRI (p<0.001) of lymphocytes. Three of the newly synthesized 1,5-BDZs exhibited positive cytogenetic activity (statistically significant reduction of SCEs, p<0,01 t-test), without showing cytostatic properties. Conclusion. The observed unexpected decrease of SCE frequency of the cultured lymphocytes due to 1,5-BDZs’ activity, in contrast to the genotoxic and cytostatic behavior of the 1,4-BDZs, is remarkable and requires further investigation in the effort to improve pharmacological effects. Keywords: cytogenetic effects, DNA, Benzodiazepines Conference: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010. Presentation Type: Oral Topic: Xenobiotic toxicity Citation: Ekonomopoulou MT, Argyraki M, Anestakis D and Iakovidou-Kritsi Z (2010). Differences in chemical structure result in opposite cytogenetic behavior of benzodiazepines. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00118 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Oct 2010; Published Online: 04 Nov 2010. * Correspondence: Dr. Maria T Ekonomopoulou, Aristotle University of Thessaloniki, Laboratory of General Biology and Genetics, Thessaloniki, Greece, biomary@med.auth.gr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Maria T Ekonomopoulou Maria Argyraki Doxakis Anestakis Zafiroula Iakovidou-Kritsi Google Maria T Ekonomopoulou Maria Argyraki Doxakis Anestakis Zafiroula Iakovidou-Kritsi Google Scholar Maria T Ekonomopoulou Maria Argyraki Doxakis Anestakis Zafiroula Iakovidou-Kritsi PubMed Maria T Ekonomopoulou Maria Argyraki Doxakis Anestakis Zafiroula Iakovidou-Kritsi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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• W2324067071 date "2010-01-01" @default.
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• W2324067071 title "Differences in chemical structure result in opposite cytogenetic behavior of benzodiazepines" @default.
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