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Home / Equine Research Bank / Int J Mol Sci / Does the Relationship Between Microelements (Copper, Zinc an...
International journal of molecular sciences2025; 26(21); 10429; doi: 10.3390/ijms262110429

Does the Relationship Between Microelements (Copper, Zinc and Selenium) and Proinflammatory Proteins (IL-6, IL-8 and Tissue Factor) Have Diagnostic Value in Equine Medicine?

Abstract: Some correlations between serum Cu, Zn and Se and cytokines have been reported in humans. Especially, the Cu:Zn ratio corresponded with inflammation. To date, relationships between microelements and proinflammatory proteins are poorly understood in horses. The aim of the study was to evaluate whether Cu, Zn and Se may influence turnover of IL-6, IL-8 and tissue factor (TF) in breeding and working horses. Blood samples obtained from 66 horses were analysed. There were 37 pregnant broodmares of different breeds, 13 barren broodmares and 16 race Thoroughbred horses. Serum Cu, Zn and Se concentration was determined using the gas flame atomic absorption spectrometry (GFAAS) method. Plasma IL-6, IL-8 and TF concentration was determined by the ELISA method. A coefficient correlation was carried out to compare the values of microelements studied with IL-6, IL-8 and TF using Pearson's test. The values of IL-6 correlated significantly positively with Se and Cu:Zn ratio, IL-8 correlated positively with Cu and Cu:Zn ratio and negatively with Zn, and TF correlated positively with Cu, Cu:Zn ratio and Se. The Cu:Zn ratio varies significantly between horses, with high values occurring in horses with high levels of proinflammatory proteins, which may indicate the presence of a subclinical inflammatory process. The high variability of TF in the studied groups gives hope for the use of its determination in laboratory diagnostics of horses.
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Publication Date: 2025-10-27 PubMed ID: 41226467PubMed Central: PMC12609903DOI: 10.3390/ijms262110429Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study explores the relationships between microelements (copper, zinc, selenium) and proinflammatory proteins (IL-6, IL-8, tissue factor) in horses.
  • It aims to determine if these relationships can be used diagnostically to detect inflammation or other health issues in equine medicine.

Background

  • In humans, copper (Cu), zinc (Zn), and selenium (Se) levels, especially the Cu:Zn ratio, have been linked to inflammation through correlations with cytokines.
  • Proinflammatory proteins like IL-6, IL-8, and tissue factor (TF) play key roles in inflammatory responses.
  • However, the interactions between these microelements and proinflammatory proteins in horses have not been well studied.

Aim of the Study

  • To assess whether microelements Cu, Zn, and Se influence the levels of IL-6, IL-8, and TF in horses.
  • To investigate if these microelements and their ratios could be diagnostic markers for inflammation in different groups of horses including broodmares (pregnant and barren) and racehorses.

Methods

  • Samples: Blood was collected from 66 horses consisting of:
    • 37 pregnant broodmares of various breeds
    • 13 barren broodmares
    • 16 Thoroughbred racehorses
  • Microelement Analysis: Serum Cu, Zn, and Se were measured using Gas Flame Atomic Absorption Spectrometry (GFAAS).
  • Proinflammatory Proteins: Plasma IL-6, IL-8, and TF concentrations were determined using ELISA tests.
  • Statistical Analysis: Pearson’s correlation coefficient was used to identify correlations between microelement levels and protein markers.

Findings

  • IL-6 showed significant positive correlations with selenium and the copper to zinc (Cu:Zn) ratio.
  • IL-8 correlated positively with copper and the Cu:Zn ratio but negatively with zinc.
  • Tissue factor (TF) correlated positively with copper, Cu:Zn ratio, and selenium.
  • The Cu:Zn ratio varied significantly among individual horses:
    • Higher Cu:Zn ratios were observed in horses with elevated levels of these proinflammatory proteins, suggesting it may indicate subclinical inflammation.
  • The variability of tissue factor levels in the study groups suggests it could be a promising marker for diagnostic use in equine medicine.

Implications

  • Microelement concentrations, particularly the Cu:Zn ratio, could serve as indirect biomarkers for inflammatory conditions in horses.
  • Monitoring such markers might help detect subclinical inflammatory states before overt symptoms appear.
  • TF shows potential as a diagnostic marker due to its variability and correlation with microelements and inflammation.
  • This research may guide veterinarians in developing better diagnostic tools based on biochemical markers rather than relying solely on clinical signs.
  • Further studies are needed to validate these markers in clinical cases and correlate them with health outcomes or specific diseases.

Conclusion

  • The study provides evidence that copper, zinc, and selenium influence proinflammatory proteins in horses.
  • The Cu:Zn ratio, along with the measurement of tissue factor and cytokines like IL-6 and IL-8, holds diagnostic value for equine inflammatory conditions.
  • This opens new possibilities for laboratory diagnostics in equine medicine to detect and monitor inflammation through blood chemistry.

Cite This Article

APA
Mojsym W, Kowalik S, Chałabis-Mazurek A, Janczarek I, Kędzierski W. (2025). Does the Relationship Between Microelements (Copper, Zinc and Selenium) and Proinflammatory Proteins (IL-6, IL-8 and Tissue Factor) Have Diagnostic Value in Equine Medicine? Int J Mol Sci, 26(21), 10429. https://doi.org/10.3390/ijms262110429

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 26
Issue: 21
PII: 10429

Researcher Affiliations

Mojsym, Wioleta
  • Department of Biochemistry, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-033 Lublin, Poland.
Kowalik, Sylwester
  • Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-033 Lublin, Poland.
Chałabis-Mazurek, Agnieszka
  • Department of Pharmacology, Toxicology and Environment Protection, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-033 Lublin, Poland.
Janczarek, Iwona
  • Department of Horse Breeding and Use, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, 20-280 Lublin, Poland.
Kędzierski, Witold
  • Department of Biochemistry, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-033 Lublin, Poland.

MeSH Terms

  • Animals
  • Horses / blood
  • Zinc / blood
  • Interleukin-8 / blood
  • Copper / blood
  • Interleukin-6 / blood
  • Selenium / blood
  • Female
  • Thromboplastin / metabolism
  • Pregnancy
  • Horse Diseases / blood
  • Horse Diseases / diagnosis
  • Inflammation / blood

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 43 references
  1. Beghelli D, Giacconi R, Mocchegiani E, Cipriano C, Malavolta M, Renieri C. A genetic variant near the equine interleukin 6 gene associated with copper:zinc ratio. Vet. J. 2011;190:e143–e145.
    doi: 10.1016/j.tvjl.2010.12.028pubmed: 21330167google scholar: lookup
  2. Fedorka CE, Scoggin KE, El-Sheikh Ali H, Troedsson MHT. Evaluating the IL-6 family of cytokines throughout equine gestation. Am. J. Reprod. Immunol. 2024;92:e13910.
    doi: 10.1111/aji.13910pubmed: 39072818google scholar: lookup
  3. Kędzierski W, Chałabis-Mazurek A, Bełkot Z, Janczarek I, Kowalik S. Zinc, copper and selenium deficiencies in broodmares in south-eastern Poland. Pol. J. Vet. Sci. 2025;28:475.
    doi: 10.24425/pjvs.2025.156074pubmed: 40996122google scholar: lookup
  4. Jacobs RD, Grum D, Trible B, Ayala DI, Karnezos TP, Gordon ME. Oral probiotic administration attenuates postexercise inflammation in horses. Transl. Anim. Sci. 2024;8:4–10.
    doi: 10.1093/tas/txae124pmc: PMC11401344pubmed: 39281311google scholar: lookup
  5. Barton MH, Collatos C. Tumor necrosis factor and interleukin-6 activity and endotoxin concentration in peritoneal fluid and blood of horses with acute abdominal disease. J. Vet. Intern. Med. 1999;13:457–464.
    doi: 10.1111/j.1939-1676.1999.tb01463.xpubmed: 10499730google scholar: lookup
  6. Wessely-Szponder J, Bełkot Z, Bobowiec R, Wójcik M, Kosior-Korzecka U. Crosstalk between adiponectin and cytokines (IL-6 and IL-8) during transportation stress in horses. Med. Weter. 2014;70:546–549.
  7. Zhang C, Xu L, Zhao Y, Wang Y. Changes in serum heavy metals in polycystic ovary syndrome and their association with endocrine, lipid-metabolism, inflammatory characteristics and pregnancy outcomes. Reprod. Toxicol. 2022;111:20–26.
    doi: 10.1016/j.reprotox.2022.05.002pubmed: 35569709google scholar: lookup
  8. Wang X, Tong J, Liang C, Wang X, Ma Y, Tao S, Liu M, Wang Y, Liu J, Yan S. Trimester-specific effects of maternal exposure to single and mixed metals on cord serum inflammatory cytokines levels: A prospective birth cohort study. Sci. Total Environ. 2023;895:165086.
    doi: 10.1016/j.scitotenv.2023.165086pubmed: 37379910google scholar: lookup
  9. Bernhard S, Hug S, Stratmann AEP, Erber M, Vidoni L, Knapp CL, Thomaß BD, Fauler M, Nilsson B, Nilsson Ekdahl K. Interleukin 8 elicits rapid physiological changes in neutrophils that are altered by inflammatory conditions. J. Innate Immun. 2021;13:225–241.
    doi: 10.1159/000514885pmc: PMC8460987pubmed: 33857948google scholar: lookup
  10. Vilotić A, Nacka-Aleksić M, Pirković A, Bojić-Trbojević Ž, Dekanski D, Jovanović Krivokuća M. IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int. J. Mol. Sci. 2022;23:14574.
    doi: 10.3390/ijms232314574pmc: PMC9738067pubmed: 36498901google scholar: lookup
  11. Gale J, Aizenman E. The physiological and pathophysiological roles of copper in the nervous system. Eur. J. Neurosci. 2024;60:3505–3543.
    doi: 10.1111/ejn.16370pmc: PMC11491124pubmed: 38747014google scholar: lookup
  12. Crutchley DJ, Que BG. Copper-induced tissue factor expression in human monocytic THP-1 cells and its inhibition by antioxidants. Circulation 1995;92:238–243.
    doi: 10.1161/01.CIR.92.2.238pubmed: 7600656google scholar: lookup
  13. Musgrave KM, Scott J, Sendama W, Gardner AI, Dewar F, Lake CJ, Spronk HMH, van Oerle R, Visser M, Ten Cate H. Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis. Thromb. Res. 2023;228:10–20.
    doi: 10.1016/j.thromres.2023.05.018pubmed: 37263122google scholar: lookup
  14. Prochazkova J, Slavik L, Ulehlova J, Prochazka M. The role of tissue factor in normal pregnancy and in the development of preeclampsia: A review. Biomed. Pap. 2015;159:192–196.
    doi: 10.5507/bp.2014.061pubmed: 25559093google scholar: lookup
  15. Girardi G, Mackman N. Tissue factor in antiphospholipid antibody-induced pregnancy loss: A pro-inflammatory molecule. Lupus 2008;17:931–936.
    doi: 10.1177/0961203308094994pmc: PMC2842117pubmed: 18827058google scholar: lookup
  16. Jawa RS, Anillo S, Huntoon K, Baumann H, Kulaylat M. Analytic Review: Interleukin-6 in Surgery, Trauma, and Critical Care: Part I: Basic Science. J. Intensive Care Med. 2011;26:3–12.
    doi: 10.1177/0885066610395678pmc: PMC6209321pubmed: 21262749google scholar: lookup
  17. Hjortoe GM, Petersen LC, Albrektsen T, Sorensen BB, Norby PL, Manda SK, Pendurthi UR, Rao LVM. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. Blood 2004;103:3029–3037.
    doi: 10.1182/blood-2003-10-3417pmc: PMC2837482pubmed: 15070680google scholar: lookup
  18. Kiouri DP, Chasapis CT, Mavromoustakos T, Spiliopoulou CA, Stefanidou ME. Zinc and its binding proteins: Essential roles and therapeutic potential. Arch. Toxicol. 2025;99:23–41.
    doi: 10.1007/s00204-024-03891-3pubmed: 39508885google scholar: lookup
  19. De K, Pal S, Prasad S, Dang AK. Effect of micronutrient supplementation on the immune function of crossbred dairy cows under semi-arid tropical environment. Trop. Anim. Health Prod. 2014;46:203–211.
    doi: 10.1007/s11250-013-0477-1pubmed: 24072427google scholar: lookup
  20. Zhang JP, Li F, Yu XW, Sheng Q, Shi XW, Zhang XW. Trace elements and cytokine profile in cytomegalovirus-infected pregnancies: A controlled study. Gynecol. Obstet. Investig. 2008;65:128–132.
    doi: 10.1159/000110013pubmed: 17957100google scholar: lookup
  21. Malavolta M, Giacconi R, Piacenza F, Santarelli L, Cipriano C, Costarelli L, Tesei S, Pierpaoli S, Basso A, Galeazzi R. Plasma copper/zinc ratio: An inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population. Biogerontology 2010;11:309–319.
    doi: 10.1007/s10522-009-9251-1pubmed: 19821050google scholar: lookup
  22. Hoffmann PR, Berry MJ. The influence of selenium on immune responses. Mol. Nutr. Food Res. 2008;52:1273–1280.
    doi: 10.1002/mnfr.200700330pmc: PMC3723386pubmed: 18384097google scholar: lookup
  23. Tomas E, Kelly M, Xiang X, Tsao T-S, Keller C, Keller P, Luo Z, Lodish H, Saha AK, Unger R. Metabolic and hormonal interactions between muscle and adipose tissue. Proc. Nutr. Soc. 2004;63:381–385.
    doi: 10.1079/PNS2004356pubmed: 15294059google scholar: lookup
  24. Akdas S, Turan B, Durak A, Aribal Ayral P, Yazihan N. The relationship between metabolic syndrome development and tissue trace elements status and inflammatory markers. Biol. Trace Elem. Res. 2020;198:16–24.
    doi: 10.1007/s12011-020-02046-6pubmed: 31993942google scholar: lookup
  25. Schneider T, Caviezel D, Korcan Ayata C, Kiss C, Niess JH, Hruz P. The copper/zinc ratio correlates with markers of disease activity in patients with inflammatory bowel disease. Crohn’s Colitis 360 2020;2:otaa001.
    doi: 10.1093/crocol/otaa001pmc: PMC7291944pubmed: 32551440google scholar: lookup
  26. Escobedo-Monge MF, Barrado E, Parodi-Román J, Escobedo-Monge MA, Torres-Hinojal MC, Marugán-Miguelsanz JM. Copper and copper/Zn ratio in a series of children with chronic diseases: A cross-sectional study. Nutrients 2021;13:3578.
    doi: 10.3390/nu13103578pmc: PMC8537994pubmed: 34684579google scholar: lookup
  27. Cappelli K, Felicetti M, Capomaccio S, Pieramati C, Silvestrelli M, Verini-Supplizi A. Exercise-induced up-regulation of MMP-1 and IL-8 genes in endurance horses. BMC Physiol. 2009;9:12.
    doi: 10.1186/1472-6793-9-12pmc: PMC2705340pubmed: 19552796google scholar: lookup
  28. Cywińska A, Turło A, Witkowski L, Szarska E, Winnicka A. Changes in blood cytokine concentrations in horses after long-distance endurance rides. Med. Weter. 2014;70:568–571.
  29. Lewandowski Ł, Kepinska M, Milnerowicz H. The copper-zinc superoxide dismutase activity in selected diseases. Eur. J. Clin. Investig. 2019;49:e13036.
    doi: 10.1111/eci.13036pubmed: 30316201google scholar: lookup
  30. Weiskirchen R, Penning LC. COMMD1, a multi-potent intracellular protein involved in copper homeostasis, protein trafficking, inflammation, and cancer. J. Trace Elem. Med. Biol. 2021;65:126712.
    doi: 10.1016/j.jtemb.2021.126712pubmed: 33482423google scholar: lookup
  31. Lappas M. Copper metabolism domain-containing 1 represses the mediators involved in the terminal effector pathways of human labour and delivery. Mol. Hum. Reprod. 2016;22:299–310.
    doi: 10.1093/molehr/gav075pubmed: 26733542google scholar: lookup
  32. Walston J, Xue Q, Semba RD, Ferrucci L, Cappola AR, Ricks M, Guralnik J, Fried LP. Serum antioxidants, inflammation, and total mortality in older women. Am. J. Epidemiol. 2006;163:18–26.
    doi: 10.1093/aje/kwj007pubmed: 16306311google scholar: lookup
  33. Ershler WB, Keller ET. Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty. Annu. Rev. Med. 2000;51:245–270.
    doi: 10.1146/annurev.med.51.1.245pubmed: 10774463google scholar: lookup
  34. Kędzierski W, Wałkuska G. Effectiveness of copper supplementation in mares during reproduction season according to the feed zinc: Copper ratio. Ann. UMCS Sect. DD 2007;62:62–69.
  35. Erez O, Romero R, Vaisbuch E, Than NG, Kusanovic JP, Mazaki-Tovi S, Gotsch F, Mittal P, Dong Z, Chaiworapongsa T. Tissue factor activity in women with preeclampsia or SGA: A potential explanation for the excessive thrombin generation in these syndromes. J. Matern. Neonatal Med. 2018;31:1568–1577.
    doi: 10.1080/14767058.2017.1320543pmc: PMC5694704pubmed: 28521572google scholar: lookup
  36. Hedia M, Ibrahim S, Mahmoud K, Ahmed Y, Ismail S, El-Belely M. Hemodynamic changes in cytokines, chemokines, acute phase proteins and prostaglandins in mares with subclinical endometritis. Theriogenology 2021;171:38–43.
    doi: 10.1016/j.theriogenology.2021.05.011pubmed: 34022530google scholar: lookup
  37. Liu IKM, Troedsson MHT. The diagnosis and treatment of endometritis in the mare: Yesterday and today. Theriogenology 2008;70:415–420.
    doi: 10.1016/j.theriogenology.2008.05.040pubmed: 18513792google scholar: lookup
  38. Sikorska U, Maśko M, Ciesielska A, Zdrojkowski Ł, Domino M. Role of Cortisol in Horse’s Welfare and Health. Agriculture 2023;13:2219.
    doi: 10.3390/agriculture13122219google scholar: lookup
  39. Antoniak S, Mackman N. Editorial Commentary: Tissue factor expression by the endothelium: Coagulation or inflammation?. Trends Cardiovasc. Med. 2016;26:304–305.
    doi: 10.1016/j.tcm.2015.12.002pubmed: 26850939google scholar: lookup
  40. Witkowski M, Landmesser U, Rauch U. Tissue factor as a link between inflammation and coagulation. Trends Cardiovasc. Med. 2016;26:297–303.
    doi: 10.1016/j.tcm.2015.12.001pubmed: 26877187google scholar: lookup
  41. Al-Hakeim HK, Al-Fadhel SZ, Al-Dujaili AH. Correlation of serum Cu and Zn with some cytokines in major depressive disorder. J. Glob. Pharma Technol. 2020;12:115–121.
  42. Maśko M, Chałabis-Mazurek A, Sikorska U, Ciesielska A, Zdrojkowski Ł, Domino M. Monthly and Pregnancy-Related Concentration of Cu and Zn in Serum of Mares in an Equine Breeding Herd. Agriculture 2024;14:35.
    doi: 10.3390/agriculture14010035google scholar: lookup
  43. Janasik B, Trzcinka-Ochocka M, Brodzka R. Oznaczanie selenu w surowicy/osoczu technika̧ spektrometrii mas z plazma̧ indukcyjnie sprzȩżona̧ (ICP-MS): Porównanie z technika̧ bezpłomieniowej absorpcyjnej spektrometrii atomowej (GF-AAS). Med. Pr. 2011;62:489–498.
    pubmed: 22312963

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