Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review

Abstract

Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms’ homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity.

Immunomodulatory Effects of Pure Cylindrospermopsin in Rats Orally Exposed for 28 Days

“…Although the effects of CYN on the immune system have been scarcely studied, it is known that it can cause immunotoxic effects in in vitro and in vivo models [2,29,30]. In this study we show for the first time the immunotoxic effects that pure CYN can cause in male and female rats orally exposed by repeated doses for 28 days to 18.75, 37.5, or 75 µg CYN/kg b.w./day, following the OECD 407 guideline [37].…”

“…Results showed that the microstructure of the jejunum was destroyed and expression levels of inflammation-related factors IL-1β, IL-8, TNF-α, and IL-10 were altered at different MC-LR concentrations. In fish, however, the number of available studies is higher [30]. The general trend for these studies is an immune-stimulative response at low MC concentrations and an immunosuppressive answer at high MC levels.…”

“…There is growing evidence that cyanotoxins may induce immunotoxicity, which should be considered due to the numerous negative changes that these disorders of immune functions may cause in organisms, including carcinogenesis [28]. However, although some authors have shown that CYN can possibly alter cells of the immune system and their functions, these studies are very scarce, as it has been recently reviewed by different authors [29,30]. Some studies have demonstrated necrosis and atrophy of the thymus and the spleen in rodents [14,15,31], followed by the first reports about the alteration of the human innate immune response in vitro due to the action of CYN [32][33][34].…”

“…Besides, the study of cytokine production and transcriptional factors would be useful to elucidate the molecular mechanisms underlying CYN immunotoxicity. In this sense, gene expression of cytokines by quantitative real-time polymerase chain reaction (RT-qPCR) is a frequently investigated parameter in most animal models, showing a dualistic response (immune-stimulative or immunosuppressive) after MCs exposure [30], but its investigation is still very scarce in the case of CYN, and limited to fish and murine cells [35,36].…”

Cyanobacteria: A Natural Source for Controlling Agricultural Plant Diseases Caused by Fungi and Oomycetes and Improving Plant Growth

“…The main genera producing toxins are Aphanizomenon, Cylindrospermopsis, Dolichospermum (previously Anabaena), Lyngbya, Microcystis, Nostoc, and Planktothrix [63]. These compounds differ in chemical structure (alkaloids, lipids, or cyclic peptides) and toxic effects (cytotoxic, dermatotoxic, hepatotoxic, and neurotoxic effects [64][65][66][67]. The cyclic peptides include microcystins and nodularins, while the alkaloids comprise anatoxin-a, anatoxin-a(S), cylindrospermopsin, saxitoxins (STXs), aplysiatoxins, and lyngbyatoxin [60].…”