Using ex vivo technologies to detect early signs of functional disorders caused by the action of industrial and household xenobiotics

Introduction. Modern toxicology faces the challenge of assessing the risks associated with prolonged exposure to low doses of industrial and household xenobiotics, as their effects are masked by the body’s compensatory mechanisms and may lead to functional and organic disorders. The purpose of this work is to evaluate the possibility of using a test system based on the assessment of activity parameters of isolated muscular organs to identify early signs of functional disorders induced by xenobiotics.

Material and methods. The experimental study was conducted on isolated hearts and lymphatic vessels of male outbred albino rats exposed to a 28‑day subchronic treatment with sodium nitrite at doses of 0.028, 0.28, and 2.8 mg/kg, and unsymmetrical dimethylhydrazine (UDMH) at doses of 0.02, 0.2, and 2.0 mg/kg. Changes in the contractile function of the isolated heart and mesenteric lymphatic vessels following xenobiotic exposure were assessed, along with the myocardial resistance to ischemia‑reperfusion.

Results. Subchronic exposure to sodium nitrite and UDMH induced cardiotoxic effects manifested as a reduction in the integral index of the isolated heart contractility. Sodium nitrite suppressed myocardial contractility without affecting the heart rate. UDMH suppressed contractility and reduced the contraction rate of both the heart and lymphatic vessels, indicating inhibition of pacemaker activity. Both xenobiotics (except for sodium nitrite at the 2.8 mg/kg dose) caused dilation of the coronary bed, reduced the minute output of the lymphatic vessels, and impaired the recovery of cardiac function after ischemia‑reperfusion.

Limitations. The results were obtained in an experimental model using male white rats subjected to subchronic administration of sodium nitrite and unsymmetrical dimethylhydrazine over a period of 28 days.

Conclusion. The combined use of ex vivo models of isolated heart and lymphatic vessels revealed early signs of functional disorders under subchronic exposure to sodium nitrite and UDMH at all tested doses. The use of this test system allows for obtaining a quantitative characterization of the cardiotoxic effect of a xenobiotic, identification of its targets, studying its potential mechanisms of action, and selecting effective agents for pharmacological correction.

Compliance with ethical standards. The study was approved by the Bioethics Commission of the Research Institute of Hygiene, Occupational Pathology and Human Ecology of the FMBA, of Russia (Conclusion No.14, dated January 22, 2026) and was carried out in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (ETS No. 123) and Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.

Authors’ contribution:
Laptev D.S. – design of the study, data processing and interpretation, writing;
Nechaykina O.V. – data collection, processing and interpretation, writing;
Petunov S.G. – study concept and design, data processing and interpretation, editing;
Bobkov D.V. – data collection, data processing, editing;
Radilov A.S. – data analysis and interpretation, editing.
All co‑authors – approval of the final version of the article, responsibility for the integrity of all its parts.

Conflict of interests. A.S. Radilov is a member of the editorial board of the journal “Toksikologicheskiy vestnik / Toxicological Review”, but he has no involvement in the decision to publish this article. The article has undergone the peer‑review procedure adopted by the journal. The authors declare that there are no apparent or potential conflicts of interest related to the publication of this article

Funding. The research was conducted as part of the state program of Russian Federation «Development of Healthcare».

Received: May 15, 2026 / Revised: July 30, 2026 / Accepted: August 3, 2026 / Published: September 16, 2026

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