Effect of arsenic oxide on mitochondrial respiration of human cells in an in vitro experiment

Introduction. This article discusses the problem of the effect of As₂O₃ on mitochondrial respiration in two types of cell cultures. Despite the fact that much has been achieved in the study of oxidative stress induced by arsenic compounds in a living organism, a number of gaps remain in understanding the mechanisms of arsenic damage to mitochondria in cells of different morphological types. In this work, a comparative analysis of the parameters of mitochondrial respiration in epithelial cells and fibroblasts exposed to different doses of As₂O₃ is carried out.

The purpose: to study the effect of As₂O₃ on mitochondrial respiration of 2 types of cells using the extracellular flow method.

Material and methods. The experiment was carried out on 2 types of human cells: fibroblast and epithelial cells. The design included 2 stages: stage 1 — dose selection according to the MTT test and cytomorphometry, stage 2 — the effect of additives that suppress or stimulate mitochondrial respiration and determine its parameters in cells exposed to different concentrations of As₂O₃.

Results. Cultures of fibroblasts and bladder epithelium differ in oxygen demand and bioenergy potential as well as in sensitivity to arsenic exposure. The calculated Bioenergetic Health Index helped reveal a dose-dependent change in mitochondrial respiration with the greatest inhibition observed at the mean dose for the fibroblast culture and at the minimum dose for bladder epithelium. The maximum dose caused an increase in the Index close to that of the control cells in both tissue cultures.

Limitations. To assess the effect of As₂O₃ on cell cultures, estimates calculated from one measured parameter of the bioenergetic function (oxygen consumption rate) were used. When conducting research, it is necessary to take into account the energy capacity of different types of cells.

Conclusion. The response of individual links of the mitochondrial respiratory chain upon exposure to arsenic depends on the cell type and the acting dose. Critical changes in mitochondrial respiration in the culture of the bladder epithelium were obtained with exposure to the minimum dose, and in the culture of fibroblasts — to the average.

Compliance with ethical standards. The study does not require the presentation of the conclusion of the biomedical ethics committee and other documents.

Authors contribution:
Gribova Y.V. — concept and design of the study, collection and processing of material, statistical analysis, writing the text, editing;
Bushueva T.V. — concept and design of the study, analysis and interpretation of results, statistical analysis, writing the text, editing;
Karpova E.P. — collection and processing of material, writing the text;
Labzova A.K. — collection and processing of material, editing;
Sakhautdinova R.R. — editing;
Gurvich V.B. — concept and design of the study, editing;
Sutunkova M.P. — concept and design of the study, editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

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

Funding. The study had no sponsorship.

Received: Jule 18, 2023 / Revised: November 11, 2023 / Accepted: March 10, 2024 / Published: April 27, 2024