Effects of cylindrospermopsin, its decomposition products, and anatoxin-a on human keratinocytes

Abstract

Toxins produced by cyanobacteria (cyanotoxins) are among the most dangerous natural compounds. In recent years, there have been many published papers related to the toxic alkaloids cylindrospermopsin (CYN) and anatoxin-a (ANTX-a), which are synthesized by several freshwater species of cyanobacteria (i.e. Raphidiopsis raciborskii and Anabaena flos-aquae) and are some of the most common cyanotoxins in aquatic reservoirs. The harmful properties of CYN are wide and primarily include cytotoxicity. To date, several analogs and decomposition products of CYN have been described, which can potentially increase its toxic effects in living organisms. The mode of action of ANTX-a is different than that observed after CYN exposure and involves structures in the nervous system. One of the most frequent situations in which cyanotoxins are introduced into the human body is by skin contact with contaminated water, i.e., during water sports, fishing or agriculture. Unfortunately, to date, knowledge on the influence of CYN, its decomposition products, and ANTX-a on human skin is limited. In this paper, we investigated the impact of CYN, its decomposition products, and ANTX-a on the proliferation of human keratinocytes, which provide a protective barrier on the skin. Moreover, we described the cytotoxic effects developed in the selected cell type and estimated the ability of the keratinocytes to migrate under the influence of the studied cyanotoxins. The obtained results suggest that CYN and its decomposition products at concentrations corresponding to that determined for CYN in nature (1 μg·mL^-1) are strong inhibitors of keratinocyte proliferation (70% inhibition within 24 h for pure CYN). The cytotoxic effects of CYN and the CYN decomposition products on keratinocytes was also significant, and the pure toxin (1 μg·mL^-1) was estimated to be 35% after 24 h of exposure. Similarly, harmful effects caused by CYN and its byproducts were observed during keratinocyte migration, and the initial form of the toxin (1 μg·mL^-1) showed 40% inhibition within 16 h. Different results were obtained for ANTX-a. The toxic effects of this compound on human keratinocytes estimated by the applied tests was observed only at the highest tested concentration (10 μg·mL^-1) and after a long period of exposure. The results presented in this paper are, to the best of our knowledge, the first description of the influence of CYN, CYN decomposition products, and ANTX-a on human epidermal cells. Clearly, CYN and its decomposition products are serious threats not only when acting on internal organs but also during the skin contact stage. Further studies on cyanotoxins should focus on the determination of their decomposition products and ecotoxicology in natural aquatic environments.

Keywords: Anatoxin-a; Cyanobacteria; Cyanotoxins; Cylindrospermopsin; Keratinocytes.