Toxicological studies. Reference intervals of mass coefficients of internal organs in a sample of 1000 rats

I.A. Lugovik, ORCID 0000-0003-3840-5049
M.N. Makarova, ORCID 0000-0003-3176-6386

Research and manufacturing company «Home оf Pharmacy»,
188663, Russia, Leningrad oblast, Vsevolozhskiy district, Kuzmolovskiy t.s., Zavodskaya st. 3-245

Е-mail: lugovik.ua@doclinika.ru

Abstract

Measuring the mass of internal organs and calculating their mass coefficients relative to body weight is a mandatory manipulation in the analysis of the toxic effects of drugs in preclinical studies. However, the assessment of the clinical significance of changes in the mass coefficients of organs can be complicated by the absence of correct intra-laboratory reference intervals that reflect normal values for the population of animals used in the research center.

The aim of this work was to generalize the results of morphometric indicators of organs obtained in previous studies on outbred rats conducted in the Research and manufacturing company «Home оf Pharmacy», from 2018 to 2020 to derive reference values of organ mass indicators of outbred rats. A retrospective analysis of data on 9 main organs used for calculating mass coefficients in toxicological studies was carried out. Analysis on a large sample of 1000 outbred rats (534 males and 466 females), with body mass ranges for males of 200 – 400 g and females of 180 – 300 g.

Reference intervals were established taking into account the recommendations of the Clinical and Laborarory Standards Institute (CLSI) for the mass coefficients of the heart, lungs, thymus, liver, spleen, kidneys, adrenal glands, brain, testes and ovaries.

It was found that in male and female rats, statistical outliers were most often observed among mass coefficients of such internal organs as the spleen (0.82 – 8.87%), adrenal glands (0 – 6.45%), lungs (0 – 5.44%), testes (0 – 4.69%) and ovaries (0 – 3.12%), outliers of other indicators were significantly less frequent. This fact should be taken into account when assessing the clinical significance of changes in these indicators.

It is advisable to have reference intervals not only for mass coefficients relative to body weight, but also to the brain, as well as to the absolute masses of organs, since in toxicological studies with significant changes in body weight, these indicators can provide more objective information.

It is expedient to form reference intervals based on mass coefficients for each span of animal body weights separately, using at least 120 animals for each span and gender. To meet these conditions, it is preferable to use an indirect method of obtaining data in a retrospective analysis in order to comply with bioethical rules.

Full text avaliable in Russain only 

Autors’ contributions

Ilia A. Lugovik – collection and analysis of material, interpretation of results, analysis of literature data, writing the text.

Marina N. Makarova – idea, revising the text. 

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