Use of a complex approach for assessment of metamizole sodium and acetylsalicylic acid toxicity, genotoxicity and cytotoxicity

• Published in: Journal of applied toxicology 2004-09, Vol.24 (5), p.401-407
• Main Authors: Arkhipchuk, V. V., Goncharuk, V. V., Chernykh, V. P., Maloshtan, L. N., Gritsenko, I. S.
• Format: Article
• Language: English
• Subjects: acetylsalicylic acid; Allium; Allium cepa; Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Aspirin - toxicity; Biomarkers - analysis; Carassius auratus gibelio; Carassius gibelio; Cell Division - drug effects; Ceriodaphnia; Ceriodaphnia affinis; Ceriodaphnia affinis; Cladocera; Dipyrone - toxicity; drug cytotoxicity; Freshwater; genotoxicity; Germination; Goldfish; Hydra; Hydra attenuata; metamizole sodium; micronucleus test; Micronucleus Tests; Mutagenicity Tests - methods; nucleolar biomarker; Water Pollutants, Chemical - toxicity
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1027

A complex approach based on the use of test organisms belonging to different systematic groups (plants, invertebrates and vertebrates), as well as the nucleolar biomarker and the micronucleus test on their cells, was applied to assess the toxicity, cytotoxicity and genotoxicity of two pharmaceutical substances (metamizole sodium and acetylsalicylic acid) applied at ic50 concentrations for mammalian cells. The compound acetylsalicylic acid was evaluated at a concentration (1.6 × 103 mg l−1) that was non‐toxic for bioassays based on fish (Carassius auratus gibelio) and hydra (Hydra attenuata) and acutely toxic for bioassays with ceriodaphnia (Ceriodaphnia affinis) and onion (Allium cepa). The metamizole sodium solution (6.25%) demonstrated acute toxicity for the whole set of test organisms. Both drugs, after their 30–360 min influence on the test organisms, first changed the nucleolar size in plant and animal cells (i.e. the transcriptional activity of ribosomal genes was affected most significantly). Moreover, the metamizole sodium solution caused nucleolar structural damage in 90% of hydra cells as early as after 30 min of exposure. The acetylsalicylic acid solution inhibited essentially the rate of cell division in the meristem of onion roots (the mitotic index decreased to 9.6‰, as compared 51.7‰ for the control). The carp incubation and the onion germination in the acetylsalicylic acid solution showed a reproducible increase in the frequency of cells with micronuclei (2 and 5.5 times, respectively) and double nuclei (3 and 1.5 times, respectively). The approach described herein may be applied for obtaining rapid, cost‐efficient and useful supplementary data on different types of toxicity for marketed drugs as well as for drugs under development. Copyright © 2004 John Wiley & Sons, Ltd.