State assessment of the rat antioxidant system’s enzymatic link in the acute pulmonotoxic exposure modeling

Introduction. Poisoning by pulmonotoxicants is an urgent problem of modern toxicology due to its frequency, severity of cases, and insufficient understanding of underlying mechanisms, which hinders effective treatment. The aim of this study is to evaluate the status of the rat antioxidant system during the modeling of acute pulmonotoxicants poisoning.

Material and Methods. Acute poisoning by pulmonotoxic substances, perfluoroisobutylene and nitrogen dioxide in toxodoses of 1.67 mg/l∙min and 5.6 mg/l∙min, respectively, was in Modeled on nonlinear male rats in an inhalation chamber with a volume of 0.2 m³ for 15 minutes. Blood and lungs samples were taken 3, 6, and 24 hours after exposure to assess the activity of superoxide dismutase, catalase, and glutathione peroxidase, while plasma levels of malondialdehyde were also measured.

Results. In response to perfluoroisobutylene exposure, superoxide dismutase, catalase, and glutathione peroxidase activities in blood after 3 h reached minimum values – 75.6 U/ml, 229.2 and 11.1 mM/(l∙min) correspondingly, with subsequent partial recovery of catalase and glutathione peroxidase activities, and compensatory increase of superoxide dismutase activity within 24 h. The lung tissue response is manifested in a decreased activity of the enzymes studied, within 24 h. Related to nitrogen dioxode exposure, the superoxide dismutase and catalase peak activities in blood were recorded after 6 h – 157.7 U/ml and 513.3 mM/(l∙min), respectively, glutathione peroxidase’s peak activity – after 3 h – 19.5 mM/(l∙min). The enzymes’ activity dynamics in lung is indicative of the superoxide dismutase level increase up to 54,5 U/ml within 24 h, while changes of catalase and glutathione peroxidase activities are characterized by minimum peak values after 6 h – 20.4 and 6.4 mM/(l∙min), respectively. There was a sustainable malondialdehyde accumulation in blood plasma during the experiment, which exceeded the corresponding value in intact group of animals.

Conclusion. These findings suggest the significant effects of free-radical oxidation processes on the pulmonotoxic agents’ toxicity mode.

Limitation. The experimental study was performed on white outbred male rats (n = 30, body weight 200-240 g), kept in a standard vivarium conditions, and randomly divided into groups with the exclusion of weakened and affected animals from the study.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the State Research and Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation, Protocol No. 18 of 16.12.2023; conducted according to the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS No. 123), European Union Directive 2010/63 EU of 22.09.2010 on the protection of animals used for scientific purposes.

Author’s contribution:
Ustinova T.M. – research concept and design, text writing, statistical data processing;
Konshakov Yu.O. – text writing;
Vengerovich N.G. – editing;
Stepanov G.S. – collecting of the material, data processing.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all parts of the article.

Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study had no sponsorship.

Received: August 8,2025 / Revised: March 4, 2026 / Accepted: March 27, 2026 / Published: April 30, 2026

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