Determining an informative value of methods for researching manifestations of long-term effects produced by acute intoxication with neurotropic toxicants in an experiment

UDC:

616-099+616.24-005.98

DOI:

10.21668/health.risk/2024.4.10.eng

Authors:

E.B. Shustov¹, M.V. Melnikovа¹, P.K. Potapov^1,2, V.A. Basharin², A.V. Belskaya¹, A.S. Melekhova¹, A.V. Ladochkina¹

Organization:

¹Golikov Research Clinical Center of Toxicology, 1 Bekhtereva St., Saint Petersburg, 192019, Russian Federation
²Military Medical Academy named after S.M. Kirov, 6 Akademika Lebedeva St., Saint Petersburg, 194044, Russian Federation

Abstract:

Information characteristics of models are rarely determined in biomedical research, which is largely due to their assessments not being mandatory, poor standardization of biomedical research, and wide variability of methods employed to model and assess a condition of animals. Nevertheless, stricter requirements to implementation of GLP standards in preclinical studies lead to an increase in importance of evaluating information indicators in toxicological and pharmacological studies.

An experimental study was accomplished on modeling long-term consequences of acute neurotoxicant poisoning. In this experiment, animals were intoxicated with model neurotoxicants. By the end of 4th week, 100 % of laboratory animals intoxicated with lead acetate and 20 % of laboratory animals intoxicated with methanol were found to have signs of long-term consequences of acute poisoning. These signs were manifested as components of psycho-organic and asthenic syndromes including impaired responses to light and an electric current stimulus, inability to perform intense physical activity in the treadmill running test, a decrease in ability to reproduce skills of passive pain avoidance.

These changes in the functional state of animals were statistically significant.

The study revealed that indicators, even those characterized by high differentiating ability (specificity) in relation to individual manifestations of long-term consequences of acute poisoning, were characterized with insufficient selectivity, accuracy and informational significance. A comprehensive assessment of the experimental model based on a criteria-based approach provides higher informational significance than the indicators taken separately. However, the discriminant model is the closest to the optimal system for detecting long-term consequences of acute poisoning with neurotropic toxicants.

Keywords:

biological modeling, intoxication, poisoning, neurotoxicant, long-term effects, lead acetate, informativeness, multifactorial analysis

Shustov E.B., Melnikovа M.V., Potapov P.K., Basharin V.A., Belskaya A.V., Melekhova A.S., Ladochkina A.V. Determining an informative value of methods for researching manifestations of long-term effects produced by acute intoxication with neurotropic toxicants in an experiment. Health Risk Analysis, 2024, no. 4, pp. 113–122. DOI: 10.21668/health.risk/2024.4.10.eng

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