Abstract
Cylindrospermopsin (CYN) is a ubiquitous cyanotoxin showing increasing incidence worldwide. CYN has been classified as a cytotoxin and, among its toxic effects, its immunotoxicity is scarcely studied. This work investigates for the first time the influence of oral CYN exposure (18.75; 37.5 and 75 µg/kg b.w./day, for 28 days) on the mRNA expression of selected interleukin (IL) genes (IL-1β, IL-2, IL-6, Tumor Necrosis Factor alpha (TNF-α), Interferon gamma (IFN-γ)) in the thymus and the spleen of male and female rats, by quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, their serum levels were also measured by a multiplex-bead-based immunoassay, and a histopathological study was performed. CYN produced immunomodulation mainly in the thymus of rats exposed to 75 μg CYN/kg b.w./day in both sexes. However, in the spleen only IL-1β and IL-2 (males), and TNF-α and IFN-γ (females) expression was modified after CYN exposure. Only female rats exposed to 18.75 μg CYN/kg b.w./day showed a significant decrease in TNF-α serum levels. There were no significant differences in the weight or histopathology in the organs studied. Further research is needed to obtain a deeper view of the molecular mechanisms involved in CYN immunotoxicity and its consequences on long-term exposures.
Highlights
Cylindrospermopsin (CYN) is currently the most studied cyanotoxin worldwide after microcystins (MCs) [1,2]
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]
The present work shows for the first time the immunotoxic effects caused by pure
Summary
Cylindrospermopsin (CYN) is currently the most studied cyanotoxin worldwide after microcystins (MCs) [1,2]. CYN has garnered increasing scientific interest because of its wide occurrence, bioaccumulation, and toxicity [3]. This alkaloid is mainly produced by Cylindrospermopsis raciborskii and Chrysosporum ovalisporum [4], and it is a stable tricyclic guanidine moiety connected by a hydroxylated bridging carbon to an uracil—the uracil moiety needed for its toxicity [5]. The occurrence of CYN and/or CYN-producing species has been reported worldwide, including temperate zones, and there is increasing concern that this toxin will represent serious human, as well as environmental, health risks across many countries [6]. Gutiérrez-Praena, D.; Jos, Á.; Pichardo, S.; Moreno, I.M.; Cameán, A.M. Presence and bioaccumulation of microcystins and cylindrospermopsin in food and the effectiveness of some cooking techniques at decreasing their concentrations: A review
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