MIR-378A-3P AS A POTENTIAL MARKER OF XENON ABUSE DETECTION IN BLOOD PLASMA DURING DOPING CONTROL

The inert gas xenon (Xe) is used in medicine as a safe and high-quality anesthetic during complex surgical interventions, as well as an antipsychotic agent. Sports medicine publications have described the properties of xenon in the recovery processes after prolonged physical training when used in xenon/oxygen (Xe/O₂) inhalations. Since 2014, xenon is in the World Anti-Doping Agency Prohibited List, in accordance with article S2 “Peptide hormones, growth factors, similar substances and mimetics” 1.2 “Hypoxia-inducible factor (HIF) activators”. MicroRNAs involved in the regulation of the HIF-signaling can be the markers to indirect determination of the abuse of HIF-activators. The aim of our work was to identify potential marker microRNAs, the alteration in expression of which could reveal the abuse of Xe in cases where the direct determination of this substance becomes practically impossible, for example, after the expiration of Xe excretion from the body. Clinical blood test were carried out on analyser SysmexXN-1000 (Germany). Isolation of miRNAs from blood plasma samples was performed using the PAXgene Blood miRNA Kit (Qiagen, USA). RT-qPCR was performed using miRCURY LNA SYBR Green PCR Kits and panels for studying the expression profiles of mature microRNAs of miRCURY LNA miRNA Focus PCR Panel (Qiagen, USA). Reference genes are included in the used panel. Statistical processing of the results was carried out using Bio-Rad CFX Maestro 3.0 software (USA). After five daily Xe/O₂ (25:75 v/v) inhalations for 30 minutes, the activation of erythropoesis, including an increase in the number of erythrocytes, an increase in hemoglobin concentration, etc., was determined. Simultaneously, the alterations in the expression profile of microRNAs circulating in blood plasma were observed. We found that the expression of hsa-miR-378a-3p in the blood plasma of volunteers after Xe/O₂ inhalation increases approximately 70 times (p<0.05) and is not detrmined at all in some volunteers before the inhalations. Thus, hsa-miR-378a-3p can be recomended as a potential candidate for the role of a marker of abuse of Xe in doping control.