Reactive oxygen and nitrogen species in the clinical medicine

Authors: Jaroslav Macášek;  Miroslav Zeman;  Marek Vecka;  Lucie Vávrová;  Jana Kodydková;  Eva Tvrzická;  Aleš Žák
Authors‘ workplace: Univerzita Karlova v Praze, 1. lékařská fakulta, IV. interní klinika VFN
Published in: Čas. Lék. čes. 2011; 150: 423-432
Category: Review Articles


Vast knowledge has accumulated recently on the role of reactive oxygen and nitrogen species (RONS) in clinical medicine. Strong evidence was disclosed on their important role in the pathogenesis of several diseases. Free radicals have unpaired electron and this is the reason for extreme reactivity causing propagation reactions that lead to the multiple damage to cells. Oxidizing agents belong to the family of reactive species. Reactive oxygen species are produced during biochemical processes such as oxidative phosphorylation, phagocytosis and metabolism of purins. Overproduction of reactive oxygen species can cause the tissue damage. Reactive nitrogen species are produced by inhibition of nitric oxide synthase by the action of asymmetric dimethylarginine. Peroxisomal oxidases, NAD(P) oxidase, xanthinoxidase, nitric oxide synthase, myeloperoxidase and lipooxygenase catalyze biochemical reactions producing reactive oxygen and nitrogen species. Biochemical and molecular processes in cells are negatively influenced by chemical modification of DNA, proteins and lipids caused by the action of reactive oxygen and nitrogen species. Antioxidant metabolites and enzymes work together to stop and to prevent oxidative modification of biomolecules. Reactive oxygen and nitrogen species play an important role in the pathogenesis of many diseases such as atherosclerosis, diabetes, hyperlipidaemia and neurodegenerative diseases.

Key words:
RONS, radicals, superoxide anion, nitric oxide radical, antioxidants, atherosclerosis, diabetes mellitus, neurodegenerative and psychiatric diseases.


1. Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signalling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 1999; 34: 879–886.

2. Sies H. Role of reactive oxygen species in biological processes. Klin Wochenschr 1991; 69(21–23): 965–968.

3. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 2004; 142: 231–255.

4. Štípek S. (ed.) Antioxidanty a volné radikály ve zdraví a nemoci. Praha: Grada Publishing 2000.

5. Valko M, Leibfritz D, Moncola J, Cronin MTD, Mazura M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem & Cell Biol 2007; 39: 44–84.

6. Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 2005; 25: 39–38.

7. Harrison R. Physiological Roles of Xanthine Oxidoreductase Drug Metab Rev 2004; 36(2): 363–375.

8. Racek J, Holeček V. Enzymy a volné radikály. Chem Listy 1999; 93: 11A–780.

9. Maritim AC, Sanders RA, Watkins JB, 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003; 17: 24–38.

10. Smith WL. The eicosanoids and their biochemical mechanisms of action. Biochem. J 1989; 259: 315–324.

11. Hazen SL, Heinecke JW. 3-chlorotyrosine, a specific marker of myeloperoxidase- catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest 1997; 99(9): 2075–2081.

12. Brennan ML, Hazen SL. Emerging role of myeloperoxidase and oxidant stress markers in cardiovascular risk assessment. Curr Opin Lipidol 2003; 14: 353–359.

13. Lawson JA, Rokach J, Fitzgerald GA. Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. J Biol Chem 1999; 274 (35): 24441–24444.

14. Stadtman ER. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radical Biol Med 1990; 9: 315–325.

15. Grune T, Reinheckel T, Davies Kja. Degradation of oxidized proteins in mammalian cells. FASEB J 1997; 11: 526–534.

16. Hensley K, Robinson KA, Gabbita SP, et al. Reactive oxygen species, cell signaling, and cell injury. Free Radic Biol Med 2000; 28(10): 1456–1462.

17. Hodgson JM, Wats GF. Can koenzyme Q10 improve vascular fiction and blood pressure? Potential for effective therapeutic reduction in vascular oxidative stress. Biofactors 2003; 18 (1–4): 129–136.

18. Heller R, Unbehaun A, Schellenberg B, et al. L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem 2001; 276(1): 40–47.

19. Vítek L, et al. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis 2002; 160(2): 449–456.

20. Piette J, Piret B, Bonini G, Schoonbroodt S, Merville MP, Legrand-Poels S, Bours V. Multiple redox regulativ in NF-kappa B transcription factor activation. Biol Chem 1997; 378 (11): 1237–1245.

21. Brunt KR, Fenrich KK, Kiani G, et al. Protection of human vascular smooth cells from H2O2-induced apoptosis through functional codependence between HO-1 and Akt. Arterioscler. Thromb. Vasc Biol 2006; 26: 2027–2034.

22. Libby P, Ridker PM, Maseri A. Inflammation and Atherosclerosis. Circulation 2002; 105: 1135–1143.

23. Griendling KK., FitzGerald GA. Oxidative stress and cardiovascular injury: Part I: Basic mechanisms and in vivo monitoring of ROS. Circulation 2003; 108: 1912–1916.

24. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996; 19: 257–267.

25. Das UN. Folic acid says NO to vascular diseases. Nutrition 2003; 19: 686–692.

26. Brownlee M. The Pathobiology of diabetic complications. A unifying mechanism. Banteng Lemure 2004. Diabetes 2005; 54: 1615–1625.

27. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993; 6: 2546–2551.

28. Guzik TJ, Mussa S, Gastaldi D, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxid synthese. Circulation 2002; 105: 1656–1662.

29. Zeman M, Žák A, Vecka M, Tvrzická E, Romaniv S, Konárková M. Treatment of hypertriglyceridemia with fenofibrate, fatty acid composition of plasma and LDL, and their relations to parameters of lipoperoxidation of LDL. Ann NY Acad Sci 2002; 967: 336–341.

30. Juurlink BH, Patison PG. Review of oxidative stress in brain and spinal cord Indry: suggestions for pharmacological and nutritional management strategies. J Spinal Cord Med 21 1998; 309–334.

31. Zhang J, Perry G, Smith MA, et al. Parkinsonęs dinase is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 1999; 154: 1423–1429.

32. Jirák R, Koukolík F. Demence. Praha: Galén 2004.

33. Perry G, Cash AD, Smith MA. Alzheimer disease and oxidative stress. J Biomed Biotechnol 2002; 23: 120–123.

34. Mahadik SP, Mukherjee S. Free radical pathology and antioxidant defense in schizophrenia: A review. Schizophrenia Research 1996; 19(1): 1–17.

35. Maziere C, Auclair M, Maziere JC. Tumor necrosis factor enhances low density lipoprotein oxidative modification by monocytes and endothelial cells. FEBS Lett 1994; 338: 43–46.

36. Tkáč I, Molčányiová A, Javorský M, Kozárová M. Fenofibrate treatment reduces circulating conjugated diene level and increases glutathione peroxidase activity. Pharmacol Res 2006; 53: 261–264.

Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management fenix.admin.empty
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account