Genotoxicity and acute toxicity of 2-amino-5-benzylthiazole in complex with polymeric nanocarrier in Allium bioassay

Abstract

Background. The search for optimal methods of selective and integral determination of various cytotoxic compounds in biological fluids and tissues, which would have high sensitivity and allow for quick and reliable assessment and detection of potentially cytotoxic components of substances with biologically active action, remains relevant today. It is known that chemotherapeutic agents can be released into the environment (air, surface water, sediments and soil) and cause adverse consequences (impact on the stability of ecosystems due to reduced viability of species). The aim of this work was to investigate the effect of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl1-benzofuran-2-carboxamide (BF1) conjugated with PEG-based polymeric nanoparticles (PEG-PN – Th1) on genotoxicity and acute toxicity in allium bioassay. Materials and Methods. Allium cepa ana-telophase assay was applied to monitor genotoxicity of the studied compounds. The acute toxic effects such as inhibition of cell division, seed germination and growth of Allium roots were estimated. A. cepa seeds (15 per each point) were germinated on the studied solutions of BF1, Th1 and Th2 (10 μM) for 5 days at 22 °C. The root growth and the percentage of inhibition of seed germination were calculated. In order to establish cyto- and genotoxicity of the studied compounds, we have determined the mitotic index and the relative amount of chromosomal aberrations. Results. BF1 had a significant inhibitory effect on root growth and seed germination at a concentration of 10 μM. The effect was eliminated when it was influenced by BF1 complex with a polymeric carrier. The free polymer does not have a negative effect on the studied parameters either. A significant decrease in the mitotic index and increase in the percentage of chromosomal aberrations was observed under the action of BF1 at a concentration of 10 µM. There was no significant change in the value of mitoitic index and percentage of chromosomal aberrations under the action of Th2 comp­lex or polymeric carrier Th1. Conclusions. The thiazole derivative in complex with a polymeric carrier at a concentration of 10 µM did not show acute toxicity in Allium cepa bioassay. Polymer carrier based on polyethylene glycol neutralized the negative effect of BF1 on the mitotic and phase indices of Allium root meristem cells; it also decreased the percentage of chromosomal aberrations.