The effects of iron injection on blood doping biomarkers in dried blood spots.
RNA-based biomarkers
blood doping
dried blood spots
iron supplementation
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
07
11
2022
received:
01
09
2022
accepted:
08
11
2022
medline:
4
4
2023
pubmed:
11
11
2022
entrez:
10
11
2022
Statut:
ppublish
Résumé
Iron supplementation is not considered as a doping method; however, it can affect the levels of several biomarkers of the hematologic module of the athlete biological passport (ABP), such as the reticulocyte percentage (%RET) and hemoglobin (HGB) level. Thus, iron injection could be a confounding factor in antidoping analyses. Previous studies have suggested that the HGB level and the expression levels of reticulocyte-related-mRNAs, such as 5'-aminolevulinate synthase 2 (ALAS2) and carbonic anhydrase 1 (CA1), could be promising biomarkers for the ABP and detectable in dried blood spots (DBSs). Therefore, in this study, we examined the impact of iron injection on the levels of these potential biomarkers in DBSs. Reticulocyte-related-mRNAs analyses were performed by RT-qPCR. Ferritin level in DBS was measured with enzyme-linked immunosorbent assay (ELISA) method. Notably, there were no significant effects of iron supplementation on the levels of ALAS2 and CA1 mRNAs but by contrast, the %RET and immature reticulocyte fraction (IRF) measured in whole blood increased significantly following iron injection. As expected, iron supplementation increased the ferritin level significantly in both serum and DBS samples. In conclusion, these findings reinforce the specificity of reticulocyte-related mRNAs in DBSs as biomarkers of blood doping to target in antidoping analyses.
Substances chimiques
Iron
E1UOL152H7
Biomarkers
0
Ferritins
9007-73-2
Hemoglobins
0
ALAS2 protein, human
EC 2.3.1.37
5-Aminolevulinate Synthetase
EC 2.3.1.37
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
444-448Subventions
Organisme : Partnership for Clean Competition
ID : # 0000000167
Informations de copyright
© 2022 John Wiley & Sons Ltd.
Références
Schumacher YO, Saugy M, Pottgiesser T, Robinson N. Detection of EPO doping and blood doping: the haematological module of the athlete biological passport: the haematological module of the athlete biological passport. Drug Test Anal. 2012;4(11):846-853. doi:10.1002/dta.406
World Anti-Doping Agency. WADA Technical Document - TD2021Bar; 2021.
Bonne TC, Lundby C, Lundby AK, Sander M, Bejder J, Nordsborg NB. Altitude training causes haematological fluctuations with relevance for the athlete biological passport: altitude training and the athlete biological passport. Drug Test Anal. 2015;7(8):655-662. doi:10.1002/dta.1757
Spodaryk K. Haematological and iron-related parameters of male endurance and strength trained athletes. Eur J Appl Physiol. 1993;67(1):66-70. doi:10.1007/BF00377707
Loria F, Cox HD, Voss SC, et al. The use of RNA-based 5′-aminolevulinate synthase 2 biomarkers in dried blood spots to detect recombinant human erythropoietin microdoses. Drug Test Anal. 2022;14(5):826-832.
Salamin O, Gottardo E, Schobinger C, et al. Detection of stimulated erythropoiesis by the RNA-based 5’-aminolevulinate synthase 2 biomarker in dried blood spot samples. Clin Chem. 2019;65(12):1563-1571. doi:10.1373/clinchem.2019.306829
Tuck MK, Chan DW, Chia D, et al. Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2009;8(1):113-117. doi:10.1021/pr800545q
Sharma A, Jaiswal S, Shukla M, Lal J. Dried blood spots: concepts, present status, and future perspectives in bioanalysis: an overview on dried blood spots. Drug Test Anal. 2014;6(5):399-414.
Cox HD, Miller GD, Lai A, Cushman D, Eichner D. Detection of autologous blood transfusions using a novel dried blood spot method. Drug Test Anal. 2017;9(11-12):1713-1720. doi:10.1002/dta.2323
Reverter-Branchat G, Ventura R, Ezzel Din M, Mateus J, Pedro C, Segura J. Detection of erythropoiesis-stimulating agents in a single dried blood spot. Drug Test Anal. 2018;10(10):1496-1507. doi:10.1002/dta.2418
Loria F, Stutz AP, Rocca A, et al. Monitoring of hemoglobin and erythropoiesis-related mRNA with dried blood spots in athletes and patients. Bioanalysis. 2022;14(5):241-251. doi:10.4155/bio-2021-0252
Ramirez Cuevas K, Schobinger C, Gottardo E, et al. Erythroferrone as a sensitive biomarker to detect stimulation of erythropoiesis. Drug Test Anal. 2020;12(2):261-267. doi:10.1002/dta.2720
Rocca A, Martin L, Kuuranne T, Ericsson M, Marchand A, Leuenberger N. A fast screening method for the detection of CERA in dried blood spots. Drug Test Anal. 2022;14(5):820-825.
Oshiro I, Takenaka T, Maeda J. New method for hemoglobin determination by using sodium lauryl sulfate (SLS). Clin Biochem. 1982;15(2):83-88. doi:10.1016/S0009-9120(82)91069-4
Loria F, Manfredi M, Reverter-Branchat G, Segura J, Kuuranne T, Leuenberger N. Automation of RNA-based biomarker extraction from dried blood spots for the detection of blood doping. Bioanalysis. 2020;12(11):729-736. doi:10.4155/bio-2020-0041
Salamin O, Mignot J, Kuuranne T, Saugy M, Leuenberger N. Transcriptomic biomarkers of altered erythropoiesis to detect autologous blood transfusion. Drug Test Anal. 2018;10(3):604-608. doi:10.1002/dta.2240
Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women-PREFER a randomized, placebo-controlled study. PLoS ONE. 2014;9(4):e94217. doi:10.1371/journal.pone.0094217
Cook JD, Flowers CH, Skikne BS. An assessment of dried blood-spot technology for identifying iron deficiency. Blood. 1998;92(5):1807-1813. doi:10.1182/blood.V92.5.1807