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

Abstract

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 ic(50) concentrations for mammalian cells. The compound acetylsalicylic acid was evaluated at a concentration (1.6 x 10(3) 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 per thousand, as compared 51.7 per thousand 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.

Subchronic effects of dipyrone on the fish species Rhamdia quelen

“…Dipyrone was considered mutagenic to various Salmonella lineage, and induced an enhanced sister-chromatid exchange in mouse bone marrow cells (Giri and Mukhopadhyay, 1998). Arkhipchuk et al (2004) evaluated the same drug as toxic and genotoxic for three organisms, belonging to three different systematic groups: Allium cepa, Ceriodaphnia affinis, Hydra attenuata and Carassius auratus gibelio.…”

Hydra, a model system for environmental studies

“…In a study investigating the toxic effects of aspiron and metamizole sodium, the latter caused nucleolar structural damage in 90 % of the Hydra cells as early as 30 min of exposure (Arkhipchuk et al, 2004). Exposure of brown and green Hydra to increasing concentration of aluminium was genotoxic as determined by the Comet assay (Kovačević, 2007).…”

Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue

“…They also underscored that the cytoprotective effect on leukocyte apoptosis occurred at concentrations that are common for the major active metabolite of the drug (8). Arkhipchuk et al (22) applied dipyrone and acetylsalicylic acid drugs to different systematic groups formed from plants, invertebrates and vertebrates. They evaluated the toxicity, cytotoxicity and genotoxicity of the drugs on those different systematic groups.…”