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

Toxins (Basel). 2022 Feb 15;14(2):144. doi: 10.3390/toxins14020144.

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.

Keywords: cylindrospermopsin; immunotoxicity; mRNA expression; rats; spleen; thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cyanobacteria Toxins / metabolism*
  • Cyanobacteria Toxins / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Female
  • Gene Expression Regulation, Bacterial / drug effects*
  • Immunomodulation / drug effects*
  • Interleukins / genetics
  • Interleukins / metabolism
  • Male
  • RNA, Messenger / drug effects*
  • Rats
  • Spleen / drug effects
  • Spleen / metabolism
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cyanobacteria Toxins
  • Interleukins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha