Experimental research of morphofunctional changes in animal internal organs upon oral ingestion of cylindrospermopsin in chronic exposure terms

Introduction. Cylindrospermopsin (CSP) is a toxin produced by a variety of cyanobacteria species in aquatic areas, increased multiplication associated with climatic changes on the planet.

A series of foreign studies indicate the possibility of CSP ingestion into the human organism both with drinking water and recreational use of lake and river water. Along with the general toxic properties of CSP revealed in experiments, the effects of its low doses on morphofunctional state of internal organs of warm-blooded animals under conditions of long-term oral intake remain poorly studied.

The aim of the study is to investigate the peculiarities of morphofunctional changes of internal organs of animals under the influence of CSP on the body of white rats at intragastric intake under conditions of chronic experiment.

Material and methods. The analytical test sample of cylindrospermopsin, manufactured in Spain, CAS 143545-90-8, was used as an experimental target, the internal organs of outbred white male rats. The toxin was injected intragastrically into male white rats at doses of 0.1 µg/kg, 1.0 µg/kg, 10.0 µg/kg daily for 90 days. Morphofunctional changes were explored using morphological, morphometric and stereometric research methods.

Results. It was found that CSP only at a dose of 10 mcg/kg under conditions of chronic oral exposure causes the following structural and functional disorders in experimental animals, the severity of which remained in comparison with the control: liver fatty degeneration by 2.1 times, micronecrosis by 80%; kidney necrotic changes in the renal glomeruli by 2 times; stomach and in the large intestine – hypersecretion of its own glands by 3.5–4 times; in the thyroid gland – desquamation of thyrocytes by 5 times; in the testes, there is a pronounced rarefaction of spermatids and spermatozoa in the absence of the control group.

Limitations. The study is limited by the conditions of intragastric intake into the body of experimental animals and the use of one species and sex of warm-blooded animals in the experiment.

Conclusion. Chronic oral exposure to CSP at a dose of 10 micrograms/kg causes significant morphofunctional changes in the internal organs of experimental animals compared with the control, with the most stimulating effects in the stomach and large intestine and structural and functional abnormalities in the testes and thyroid gland, as well as necrotic disorders in the liver and kidneys.

Compliance with ethical standards. A positive conclusion was received from the Commission on Biomedical Ethics of the Federal Scientific Center of Hygiene named after F.F. Erisman (Protocol No. 03/22 dated 11/21/2022).

Authors’ contribution:
Kuz N.V. – conception and design of the study, collection and processing of material;
Turbinskii V.V. – research concept and design, text writing, editing;
Pushkareva M.V. – research concept and design, summary of results, text writing, editing;
Sinitsyna O.O. – research concept and design, summary of results, editing;
Masaltsev G.V. – text writing and material processing;
Shiryaeva M.A., Ryashentseva T.M., Vostrikova M.V., Malinovskaya N.N., Belyaeva N.N. – collection and processing of the material.
All co-authors – responsibility for the integrity of all parts of the article, approval of the final version of the article.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgments. The study was carried out as part of the implementation of the state program “Ensuring Chemical and Biological Safety of the Russian Federation” for 2021–2027.

Received: February 27, 2025 / Revised: May 27, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

1. Voloshko L.N., Plyushch A.V., Titova N.N. Toxins of cyanobacteria (cyanobacteria, cyanophyta). Algologiya. 2008; 18(1): 3–20.

2. Falconer I.R. An overview of problems caused by toxic blue-green algae (cyanobacteria) in drinking and recreational water. Environmental Toxicology: An International Journal 1999; 14(1): 5–12.

3. Falconer I.R. Toxic cyanobacterial bloom problems in Australian waters: risks and impacts on human health. Phycologia. 2001; 40(3): 228–33.

4. Falconer I.R., Humpage A.R. Cyanobacterial (blue‐green algal) toxins in water supplies: Cylindrospermopsins. Environmental Toxicology: An International Journal. 2006; 21(4): 299–304.

5. Seawright J. Testing for necessary and/or sufficient causation: Which cases are relevant? Political Analysis. 2002; 10 (2): 178–93.

6. Shaw G.R. et al. Cylindrospermopsin, a cyanobacterial alkaloid: evaluation of its toxicologic activity. Therapeutic Drug Monitoring. 2000; 22(1): 89–92.

7. Chernoff N., Hill D.J., Chorus I., Diggs D.L., Huang H., King D., Lang J.R., Le T.-T., Schmid J.E., Travlos G.S., et al. Cylindrospermopsin toxicity in mice following a 90-d oral exposure. J. Toxicol. Environ. Health Part A. 2018; 81: 549–66. https://doi.org/10.1080/15287394.2018.1460787

8. Belyaeva N.N., Rakitsky V.N., Nikolaeva N.I., Vostrikova M.V., Veschemova T.E. Quantitative structural and functional evaluation of various systems of the organism of laboratory animals in hygienic research. Gigiena I Sanitariya. 2020; 99(12): 1438–45. https://doi.org/10.47470/0016-9900-2020-99-12-1438-1445

9. Khalafyan A.A. Statistica 6. Statistical data analysis [Statistica 6. Statisticheskij analiz dannyh]. Moscow: 6LLC “Binom-Press”; 2007.

10. Poniedziałek B., Rzymski P., Kokociński M. Cylindrospermopsin: Water-linked potential threat to human health in Europe. Environ. Toxicol.Pharm. 2012; 34: 651–60. https://doi.org/10.1016/j.etap.2012.08.005

11. Hinojosa M.G., Prieto A.I., Muñoz-Castro C., Sánchez-Mico M.V., Vitorica J., Cameán A.M., Jos Á. Cytotoxicity and Effects on the Synapsis Induced by Pure Cylindrospermopsin in an E17 Embryonic Murine Primary Neuronal Culture in a Concentration- and Time-Dependent Manner. Toxins (Basel). 2022; 14(3): 175. https://doi.org/10.3390/toxins14030175

12. Guzmán-Guillén R., Lomares I., Moreno I.M., Prieto A.I., Moyano R., Blanco A., Cameán A.M. Cylindrospermopsin induces neurotoxicity in tilapia fish (Oreochromis niloticus) exposed to Aphanizomenon ovalisporum. Aquat. Toxicol. 2015; 161: 17–24. https://doi.org/10.1016/j.aquatox.2015.01.024