Cytotoxic and Genotoxic Effects of Cyanobacterial and Algal Extracts—Microcystin and Retinoic Acid Content

Abstract

In the last decade, it has become evident that complex mixtures of cyanobacterial bioactive substances, simultaneously present in blooms, often exert adverse effects that are different from those of pure cyanotoxins, and awareness has been raised on the importance of studying complex mixtures and chemical interactions. We aimed to investigate cytotoxic and genotoxic effects of complex extracts from laboratory cultures of cyanobacterial species from different orders (Cylindrospermopsis raciborskii, Aphanizomenon gracile, Microcystis aeruginosa, M. viridis, M. ichtyoblabe, Planktothrix agardhii, Limnothrix redekei) and algae (Desmodesmus quadricauda), and examine possible relationships between the observed effects and toxin and retinoic acid (RA) content in the extracts. The cytotoxic and genotoxic effects of the extracts were studied in the human hepatocellular carcinoma HepG2 cell line, using the MTT assay, and the comet and cytokinesis-block micronucleus (cytome) assays, respectively. Liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) was used to detect toxins (microcystins (MC-LR, MC-RR, MC-YR) and cylindrospermopsin) and RAs (ATRA and 9cis-RA) in the extracts. Six out of eight extracts were cytotoxic (0.04–2 mgDM/mL), and five induced DNA strand breaks at non-cytotoxic concentrations (0.2–2 mgDM/mL). The extracts with genotoxic activity also had the highest content of RAs and there was a linear association between RA content and genotoxicity, indicating their possible involvement; however further research is needed to identify and confirm the compounds involved and to elucidate possible genotoxic effects of RAs.

Anabaenopeptins: What We Know So Far

“…These microorganisms produce a great variety of bioactive compounds, which have been investigated mainly due to their biotechnological potential and environmental relevance [ 1 , 2 , 3 ]. Cyanotoxins are among the most studied compounds originated from cyanobacteria since they are capable of negatively affecting human and animal health [ 4 , 5 ]. These metabolites can vary drastically concerning their action mechanism and chemical structure, which include peptides, alkaloids, and lipopolysaccharides [ 6 , 7 , 8 ].…”

Cyanobacterial Harmful Algal Blooms in Aquatic Ecosystems: A Comprehensive Outlook on Current and Emerging Mitigation and Control Approaches

“…Here, we highlight an emerging venue based on intra- and inter-species communication/competition/allopathic interactions that take place between toxic cyanobacteria, non-toxic cyanobacteria (mainly Microcystis sp. ), and other organisms, mainly (but not only) green algae, that may ultimately lead to the development of mitigation protocols (see [ 66 , 75 , 89 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 ] and references therein). An emerging example is the reduction of cyanoHAB populations that enables the persistence dominance of various non-toxic algae.…”

Identification of Novel Molecular Targets of Four Microcystin Variants by High-Throughput Virtual Screening

“…MCs induce DNA damage, mitochondrial dysfunction, cytoskeleton disruption, endoplasmic reticulum disruption, and cell cycle dysregulation, among other processes [4,14,15]. The different toxic effects of MCs appear to be dose-and time-dependent.…”

“…MCs induce DNA damage, mitochondrial dysfunction, cytoskeleton disrupti doplasmic reticulum disruption, and cell cycle dysregulation, among other pr [4,14,15]. The different toxic effects of MCs appear to be dose-and time-dependent ever, the molecular factors that induce the different biochemical and cellular effec not been fully elucidated [12,15].…”