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Changes in metallothionein levels in patients with malignant prostate cancer – a pilot study


Authors: L. Melich 1;  J. Raja 1;  L. Vysloužilová 2;  O. Štěpánková 2;  J. Čepová 1;  M. Fořtová 1;  K. Kotaška 1;  E. Klapková 1;  J. Werle 1;  R. Průša 1;  R. Kizek 1
Authors‘ workplace: 2. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice v Motole, Praha Ústav lékařské chemie a klinické biochemie, Přednosta: prof. MUDr. Richard Průša, CSc. 1;  České vysoké učení technické v Praze, Český institut informatiky, robotiky a kybernetiky Oddělení biomedicínského inženýrství a asistivní technologie, Vedoucí oddělení: prof. RNDr. Olga Štěpánková, CSc. 2
Published in: Prakt. Lék. 2023; 103(6): 299-303
Category: Of different specialties

Overview

Aim: To analyse concentrations of metallothionein (MT) in urine samples of patients diagnosed with prostate cancer (CaP).
Methods: Samples were electrochemically analysed by difference pulse voltametry (DPV) method in Brdička’s buffer. Acquired data were then evaluated as an area under the curve (AUC). Concentrations of MT were determinedby calibration curve method.
Results: Metallothioneins are proteins with molecular weight about 10 kDa. Theirbiological significance lies in maintaining homeostasis of metal ions. Their analytical determination is complicated. One of the most effective determination methods is by electrochemistry. Previously mentioned methods were used tostudy the changes of MT concentrations of patients with CaP, and with benign prostate hyperplazia (BHP). Our pilotexperiment determined concentrations of MT in a) healthy controls (n = 13) was 2.9 ± 1.2 µg/mmol of creatinine, b) BHP was 4.7 ± 1.7 μg/mmol of creatinine, c) CaP group (n = 9) was 6.7 ± 1.5 µg/mmolof creatinine. Difference between healthy controls and CaP group was statistically significant (p = 0.0099). Differencebetween BHP and CaP group was also determined (p = 0.0928). Difference between BHP and healthy controls is notvery statistically significant (p = 0.7869).
Conclusion: We were able to demonstrate differences between healthycontrols, BHP patients and CaP patients.Concentrations of MT in CaP patients were elevated, but they need to be studied in more detail.

Keywords:

oxidative stress – thiol compounds – metallomics – electrochemical methods


Sources
  1. Binz PA, Kagi JHR. Metallothionein: Molecular evolution and classification. In: Klaassen CD. (eds). Metallothionein IV. Advances in Life Sciences. Basel: Birkhäuser 1999.
  2. Kizek R, Trnkova L and Palecek E. Determination of metallothionein at the femtomole level by constant current stripping chronopotentiometry. Anal Chem 2001; 73(20): 4801–4807.
  3. Ruttkay-Nedecky B, Nejdl L, Gumulec J, et al. The role of metallothionein in oxidative stress. Int J Mol Sci 2013; 14(3): 6044–6066.
  4. Krizkova S, Fabrik I, Adam V, et al. Metallothionein – a promising tool for cancer diagnostics. Brat Med J 2009; 110(2): 93–97.
  5. Kruseova J, Hynek D, Adam V, et al. Serum metallothioneins in childhood tumours – a potential prognostic marker. Int J Mol Sci 2013; 14(6): 12170–12185.
  6. Martinez VA, Serrat N, Paternain JL, et al. Zinc and metallothionein metabolism in nephrotic syndrome. Trace Elem Electrolyt 1996; 13(1): 14–17.
  7. Chen L, Jin TY, Huang B, et al. Critical exposure level of cadmium for elevated urinary metallothionein – An occupational population study in China.Toxicol Appl Pharmacol 2006; 215(1): 93–99.
  8. Kido T, Shaikh Z A, Kito H, et al. Dose–response relationship between urinary cadmium and metallothionein in a japanese population environmentally exposed to cadmium. Toxicology 1991; 65(3): 325–332.
  9. Nakajima M, Kobayashi E, Suwazono Y, et al. Excretion of urinary cadmium, copper, and zinc in cadmium–exposed and nonexposed subjects, with special reference to urinary excretion of beta(2)-microglobulin and metallothionein. Biol Trac Elem Res 2005; 108(1–3): 17–31.
  10. Kotoh S, Naito S, Sakamoto N, et al. Metallothionein expression is correlated with cisplatin resistance in transitional-cell carcinoma of the urinary-tract. J Urol 1994; 152(4): 1267–1270.
  11. Zimmerman AW, Horak E, Banta JV, et al. Urinary-excretion of zinc and metallothionein in children with spina-bifida. Annal Neurol 1983; 14(3): 385–385.
  12. Sabolic I, Breljak D, Skarica M, et al. Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals 2010; 23(5): 897–926.
  13. Krizkova S, Masarik M, Kukacka J. Serum metallothionein in newly diagnosed patients with childhood solid tumours. Acta Biochim Pol 2010; (57): 561–566.
  14. Petrlová J, Blaštík O, Průša R, a kol. Analýza obsahu metalothioneinu u pacientů se zhoubným nádorem prsu, tlustého střeva nebo maligním melanomem. Klin Onkol 2006; 19(2): 138–142.
  15. Fabrik I, Adam V, Křížková S, a kol. Určení hladiny termostabilních thiolů u pacientů se zhoubným nádorem. Klin Onkol 2007; 20(6): 384–389.
  16. Fabrik I, Kukačka J, Adam V, a kol. Metalothionein a jeho vztah k protinádorové léčbě na bázi platinových komplexů. Prakt. Lék. 2008; 88(2): 90–93.
  17. Raudenská M, Šmerková K, Tanhäuserová V, a kol. Metalothionein a jeho role v detoxikaci těžkých kovů a predispozici k chorobám. Prakt. Lék. 2012; 92(6): 322–326.
  18. Lobinski R, Chassaigne H, Szpunar J. Analysis for metallothioneins using coupled techniques. Talanta 1998; 46(2): 271–289.
  19. Brdicka R. Application of the polarographic effect of proteins in cancer diagnosis. Nature 1937; 139: 330.
  20. Olafson RW, Olsson PE. Electrochemical detection of metallothionein. Methods Enzymol 1991; 205: 205–213.
  21. Raspor J, Pavicic B. Electrochemical methods for quantification and characterization of metallothioneins induced in Mytilus galloprovincialis. Fresenius J Anal Chem 1996; 354: 529–534.
  22. Petrlová J, Potěšil D, Mikelová R, et al. Attomole voltammetric determination of metallothionein. Electrochim Acta 2006; 51(24): 5112–5119.
  23. Skoták V, Sehnal K, Banáš D, a kol. Využití Brdičkovy reakce pro detekci metalothioneinu v moči. Czech Chem Soc Symp Ser 2020; 18: 4P–08: 131.
  24. Melich L, Fořtová M, Hosnedlová B, a kol. Studium hladiny metalothionienu v séru pacientů se zhoubným nádorem. Chem Listy 2023; 117(10): 573–580.
  25. Hubaux A, Vos G. Decision and detection limits for linerar calibration curves. Anal Chem 1970; 42(8): 849–851.
  26. Brdicka R. Polarographic investigation in serological cancer diagnosis. Nature 1937; 139: 1020–1021.
  27. Dabrio M, Rodríguez AR, Bordin G, et al. Recent developments in quantification methods for metallothionein. J Inorg Biochem 2002; 88(2): 123–134.
  28. Skoták V. Elektrochemická detekce metalothioneinu v moči a jeho vztah k zhoubnému nádoru prostaty. Gymnázium Boskovice:Středoškolská odborná činnost 2021; 1–31.
  29. Olafson RW. Electrochemical characterization of metallothionein metal mercaptide complexes – Application of cyclic voltammetry to investigation of metalloproteins. Bioelectrochem Bioenerg 1988; 19(1): 111–125.
  30. Folch J, Ortega A, Cabre A, et al. Urinary levels of metallothioneins and metals in subjects from a semiindustrialized area in Tarragona Province of Spain. Biol Trace Elem Res 1998; 63(2): 113–121.
  31. Zimmerman AW, Garvey JS, Banta JV, et al. Urinary zinc and metallothionein in children with spina bifida. Ped Neurol 1985; 1(1): 23–27.
  32. Tohyama C, Shaikh ZA, Nogawa K, et al. Urinary metallothionein as a new index of renal dysfunction in „ltai-ltai“ disease patients and otherJapanese women environmentally exposed to cadmium. Arch Toxicol 1982; (50): 159–166.
  33. Dziegiel P, Pula B, Kobierzycki C, et al. Metallothioneins in normal and cancer cells. Adv Anat Embryol Cell Biol 2016; 218: 1–117.
  34. Coyle P, Philcox JC, Carey LC, et al. Metallothionein: The multipurpose protein. Cell Mol Life Sci 2002; 59(4): 627–647.
  35. Nordberg GF, Garvey JS, Chang CC. Metallothionein in plasma and urine of cadmium workers. Environment Res 1982; 28(1): 179–182.
  36. Bordin G, Raposo FC, Rodriguez A. Mammalian metallothionein sub-isoform separation by RP-HPLC with online UV and electrochemical detection. In: Klaassen CD. (eds) Metallothionein IV. Advances in Life Sciences. Basel: Birkhäuser 1999.
  37. Bordin G, Cordeiro-Raposo F, Rodriguez AR. Study of mammalian metallothionein polymorphism by reverse phase HPLC with on-linediode array and electrochemical detection. J Liq Chrom Rel Technol 2000; 23(7): 999–1018.
  38. Miyairi S, Shibata S and Naganuma A. Determination of metallothionein by high-performance liquid chromatography with fluorescence detection using an isocratic solvent system. Anal Biochem 1998; 258(2): 168–175.

adresa pro korespondenci:
prof. Ing. René Kizek, Ph.D., DrSc., MBA
Ústav lékařské chemie aklinické biochemie
2. LF UK a FN Motol
V Úvalu 84, 150 06 Praha 5
e-mail:
kizekrene@gmail.com

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