Homeostaza redoks sistema, oksidativni stres i antioksidativni sistem u zdravlju i bolesti: mogućnost modulacije antioksidansima

  • Jelena Kotur-Stevuljević Univerzitet u Beogradu – Farmaceutski fakultet, Katedra za medicinsku biohemiju
  • Jelena Savić Univerzitet u Beogradu – Farmaceutski fakultet, Katedra za farmaceutsku hemiju
  • Milena Simić Univerzitet u Beogradu – Farmaceutski fakultet, Katedra za organsku hemiju
  • Jasmina Ivanišević Univerzitet u Beogradu – Farmaceutski fakultet, Katedra za medicinsku biohemiju
DOI: https://doi.org/10.5937/arhfarm73-45369
Ključne reči: antioksidansi, prooksidansi, slobodni radikali, enzimska antioksidativna zaštita

Sažetak


Redoks disbalans se javlja kada činioci oksidativnog stresa – prooksidansi – nadvladaju mehanizme antioksidativne zaštite. U stanju zdravlja, homeostatski mehanizmi obezbeđuju uravnoteženo stvaranje slobodnih radikala i čitave serije antioksidanasa koji su zaduženi za njihovo bezbedno uklanjanje. Stvaranje slobodnih radikala je deo fizioloških procesa u zdravom organizmu; neki od njih su specifični signalni molekuli i u tim procesima su njihovo prisustvo i aktivnost neophodni. U različitim bolestima kao što su kancer, KVB, dijabetes, autoimunske bolesti, reumatske bolesti, sistemski lupus, kožne bolesti, stvaranje slobodnih radikala nadvladava mehanizme zaštite, pa se razvija „oksidativni stres“ koji oštećuje ćelije i tkiva. Da bi se sprečilo štetno delovanje slobodnih radikala, u ćeliji postoji sistem enzimske antioksidativne zaštite, koga čine: superoksid-dismutaza (SOD), glutation-peroksidaza (GSHPx), glutation-reduktaza (GR), glutaredoksin, redukovani/oksidovani glutation (GSH/GSSG) i tioredoksin (TRX). Primeri neenzimskih antioksidanasa su: antioksidativni vitamini kao što su A, C i E, dihidrolipoinska kiselina, metalotioneini, ceruloplazmin, koenzim Q10, urea, kreatinin, itd. Redoks ravnoteža je pod uticajem cirkadijalnog ritma i spoljašnjih faktora koji čine „ekspozom“ i uključuju način ishrane i životne navike. Suplementacija antioksidansima je postala sve popularnija praksa za održavanje optimalne funkcije organizma. Neki od antioksidanasa ispoljavaju prooksidantnu aktivnost i zato je važno da njihova primena bude kontrolisana. Veza između redoks statusa organizma i delovanja antioksidanasa omogućava razvoj multidisciplinarnih istraživanja u kojima se povezuju biohemija, molekularna biologija, nauka o ishrani, hemija prirodnih proizvoda i sama klinička praksa. 

Reference

1.  Sies H. Oxidative Stress: Concept and Some Practical Aspects. Antioxidants. 2020;9:852.

2.      Casas AI, Dao VT, Daiber A, Maghzal GJ, Di Lisa F, Kaludercic N, et al. Reactive Oxygen-Related Diseases: Therapeutic Targets and Emerging Clinical Indications. Antioxid Redox Signal. 2015;23:1171-1185.

3.      Frijhoff J WPG, Stocker R, Cheng D, Davies SS, Knight A, Taylor E, et al. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal. 2015;23:1144–1170.

4.      Halliwell B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol. 2006;141:312-322.

5.      Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front Physiol. 2020;11:694.

6.      Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal. 2008;10:1343-1374.

7.      Kotur-Stevuljević J, Spasić S, Jelić-Ivanović Z, Spasojević-Kalimanovska V, Stefanović A, Vujović A, et al. PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients. Clin Biochem. 2008;41:1067-1073.

8.      Kotur-Stevuljević J, Memon L, Stefanović A, Spasić S, Spasojević-Kalimanovska V, Bogavac-Stanojević N, et al. Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients. Clin Biochem. 2007;40:181-187.

9.      Kotur-Stevuljević J, Spasić S, Stefanović A, Zeljković A, Stanojević-Bogavac A, Kalimanovska-Oštrić D, et al.  Paraoxonase-1 (PON1) activity, but not PON1 Q192R phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population. Clin Chem Lab Med. 2006;44:1106-1113.

10.  Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. 5th ed. Oxford: Oxford Academic; 2015. Online ed. doi: 10.1093/acprof:oso/9780198717478.001.0001.

11.  Dröge W. Free Radicals in the Physiological Control of Cell Function. Physiol Rev. 2002;82:47-95.

12.  Berlett B, Stadtman E. Protein Oxidation in Aging, Disease and Oxidative Stress. J Biol Chem. 1997;272:20313-20316.

13.  Borza C, Muntean D, Dehelean C, Savoiu G, Serban C, Simu G, et al. Oxidative Stress and Lipid Peroxidation – A Lipid Metabolism Dysfunction. Lipid Metabolism. InTech. doi: 10.5772/51627.

14.  Gonzalez-Hunt C, Wadhwa M, Sanders L. DNA damage by oxidative stress: Measurement strategies for two genomes. Curr Opin Toxicol. 2018;7:87-94.

15.  Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763.

16.  Halliwell B. The antioxidant paradox: less paradoxical now? Br J Clin Pharmacol. 2013;75:637-644.

17.  Mattson MP, Cheng A. Neurohormetic phytochemicals: low‐dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 2006;29:632–639.

18.  Ayoka TO, Ezema BO, Eze CN, Nnadi CO. Antioxidants for the Prevention and Treatment of Non-communicable Diseases. J Explor Res Pharmacol. 2022;7:178-188.

19.  Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y.  Oxidative stress and diabetes: antioxidative strategies. Front Med. 2020;14:583–600.

20.  Howden R. Nrf2 and cardiovascular defense. Oxid Med Cell Longev. 2013;2013:104308.

21.  Tavakoli R, Tabeshpour J, Asili J, Shakeri A, Sahebkar A. Cardioprotective Effects of Natural Products via the Nrf2 Signaling Pathway. Curr Vasc Pharmacol. 2021;19(5):525-541.

22.  Davies JMS, Cillard J, Friguet B, Cadenas E, Cadet J, Cayce R, et al. The Oxygen Paradox, the French Paradox, and age-related diseases. Geroscience. 2017;39:499-550.

23.  Goszcz K, Deakin SJ, Duthie GG, Stewart D, Leslie SJ, Megson IL. Antioxidants in cardiovascular therapy: panacea or false hope? Front Cardiovasc Med. 2015;2:29.

24.  Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79:727–747.

25.  Otręba M, Kośmider L, Stojko J, Rzepecka-Stojko A. Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review. Molecules. 2020;25:5343.

26.  Wang M, Simon JE, Aviles IF, He K, Zheng Q, Tadmor Y. Analysis of Antioxidative Phenolic Compounds in Artichoke (Cynara scolymus L.). J Agric Food Chem. 2003;51:601−608.

27.  Crevar-Sakac M, Vujić Z, Kotur-Stevuljević J, Ivanisević J, Jelić-Ivanović Z, Milenković M, et al. Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats. Vojnosanit Pregl. 2016;73:178-187.

28.  Ogier N, Amiot M, Georgé S, Maillot M, Mallmann C, Maraninchi M, et al. LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia. Eur J Nutr. 2013;52:547−557.

29.  Irazabal MV, Torres VE. Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease. Cells. 2020;9:1342.

30.  Kotur-Stevuljevic J, Simic-Ogrizovic S, Dopsaj V, Stefanovic A, Vujovic A, Ivanic-Corlomanovic T, et al. A hazardous link between malnutrition, inflammation and oxidative stress in renal patients. Clin Biochem. 2012;45:1202-1205.

31.  Ta MH, Schwensen KG, Liuwantara D, Huso DL, Watnick T, Rangan GK. Constitutive renal Rel/nuclear factor-kappaB expression in Lewis polycystic kidney disease rats. World J Nephrol. 2016;5:339–357.

32.  Aranda-Rivera AK, Cruz-Gregorio A, Pedraza-Chaverri J, Scholze A. Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls. Antioxidants. 2022;11:1112.

33.  Ghosh S, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, et al. Curcumin ameliorates renal failure in 5/6 nephrectomized rats: Role of inflammation. Am J Physiol Ren Physiol. 2009;296:F1146–F1157.

34.  Kostić K, Brborić J, Delogu G, Simić MR, Samardžić S, Maksimović Z, et al. Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls. Molecules. 2023;28:2646.

35.  Eugenio-Pérez D, Medina-Fernández LY, Saldivar-Anaya JA, Molina-Jijón E, Pedraza-Chaverri J. Role of Dietary Antioxidant Agents in Chronic Kidney Disease. Free Radicals and Diseases. InTech. doi: 10.5772/63669.

36.  Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005;4:5.

37.  Stefanovic A, Kotur-Stevuljevic J, Spasic S, Vekic J, Zeljkovic A, Spasojevic-Kalimanovska V, Jelic-Ivanovic Z. HDL 2 particles are associated with hyperglycaemia, lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients. Clin Biochem. 2010;43:1230-1235.

38.  Ma X, Chen Z, Wang L, Wang G, Wang Z, Dong X, et al. The Pathogenesis of Diabetes Mellitus by Oxidative Stress and Inflammation: Its Inhibition by Berberine. Front Pharmacol. 2018;9:782.

39.  Xie X, Chang X, Chen L, Huang K, Huang J, Wang S, et al. Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling. Mol Cell Endocrinol. 2013;381:56-65.

40.  Zhu X, Guo X, Mao G, Gao Z, Wang H, He Q, Li D. Hepatoprotection of berberine against hydrogen peroxide-induced apoptosis by upregulation of Sirtuin 1. Phytother Res. 2013;27(3):417-21.

41.  Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Gen Develop. 1999;13:76–86.

42.  Zhang X, Liang D, Lian X, Jiang Y, He H, Liang W, et al. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism. Apoptosis. 2016;21:721-736.

43.  Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y. Oxidative stress and diabetes: antioxidative strategies. Front Med. 2020;14:583–600.

Objavljeno
2023/08/30
Broj časopisa
Vol. 73 Br. Notebook 4 (2023): Arhiv za farmaciju
Rubrika
Pregledni (Revijalni) rad
Autori koji objavljuju u ovom časopisu pristaju na sledeće uslove:

  1. Autori zadržavaju autorska prava i pružaju časopisu pravo prvog objavljivanja rada i licenciraju ga "Creative Commons Attribution licencom" koja omogućava drugima da dele rad, uz uslov navođenja autorstva i izvornog objavljivanja u ovom časopisu.

  2. Autori mogu izraditi zasebne, ugovorne aranžmane za neekskluzivnu distribuciju članka objavljenog u časopisu (npr. postavljanje u institucionalni repozitorijum ili objavljivanje u knjizi), uz navođenje da je članak izvorno objavljen u ovom časopisu.

  3. Autorima je dozvoljeno i podstiču se da postave objavljeni članak onlajn (npr. u institucionalni repozitorijum ili na svoju internet stranicu) pre ili tokom postupka prijave rukopisa, s obzirom da takav postupak može voditi produktivnoj razmeni ideja i ranijoj i većoj citiranosti objavljenog članka (Vidi Efekti otvorenog pristupa).