reviews - Dental and Medical Problems

2 downloads 0 Views 136KB Size Report
3 Department of Conservative Dentistry Medical University, Bialystok, Poland ... Med. Probl. 2013, 50, 4, 461–466). Key words: antioxidants, oxidative stress, ...
REVIEWS Dent. Med. Probl. 2013, 50, 4, 461–466 ISSN 1644-387X

© Copyright by Wroclaw Medical University and Polish Dental Society

Małgorzata Knaś1, A, B, E, F, Mateusz Maciejczyk2, B, F, Danuta Waszkiel3, A, Anna Zalewska3, E, F

Oxidative Stress and Salivary Antioxidants Stres oksydacyjny i antyoksydanty śliny Institut of Health Care, Higher Vocational School, Suwalki, Poland Students Scientific Group “Stomatological Biochemistry” at the Department of Conservative Dentistry Medical University, Bialystok, Poland 3 Department of Conservative Dentistry Medical University, Bialystok, Poland 1 2

A – concept, B – data collection, C – statistics, D – data interpretation, E – writing/editing the text, F – compiling the bibliography

Abstract Oxidative stress is caused by a shift in the balance between highly reactive molecules, such as reactive oxygen species, and antioxidant body’s defense system. Reactive oxygen species play a pivotal role in the human body and are produced by a living organism as a result of normal cellular metabolism and environmental factors, such as pollutants and cigarette smoke. However, their high activity might have important biological consequences. ROS can be considered as a  significant mediator of damage to major biomolecules and cell structures. It is also well documented that oxidative stress takes part in a  growing number of pathological states and diseases, especially when inflammation is prominent. Aerobic organisms have developed an antioxidant system and are effective in opposing the effect of ROS. These antioxidants can be divided into the following: enzymatic and non-enzymatic. In pathological conditions the antioxidant system may be overwhelmed, which leads to oxidative stress. The purpose of this mini-review is to introduce the important findings concerning the ROS and salivary antioxidants (Dent. Med. Probl. 2013, 50, 4, 461–466). Key words: antioxidants, oxidative stress, reactive oxygen species, saliva.

Streszczenie Stres oksydacyjny jest spowodowany przesunięciem równowagi między aktywnością wysoce reaktywnych cząsteczek (np.: reaktywnym tlenem) a przeciwutleniającym systemem obronnym organizmu. Reaktywne formy tlenu pełnią zasadniczą rolę w ludzkim organizmie i są wytwarzane przez żywe organizmy w wyniku normalnego metabolizmu komórkowego oraz na skutek czynników środowiskowych (dym papierosowy, zanieczyszczenia). Ich duża aktywność może mieć jednak istotne konsekwencje biologiczne. ROS są uważane za istotny mediator uszkodzenia ważnych cząsteczek biologicznych i  struktur komórkowych. Jest również dobrze udokumentowane, że stres oksydacyjny bierze udział w  coraz większej liczbie stanów patologicznych i  chorób, zwłaszcza gdy stan zapalny jest bardzo widoczny. Organizmy tlenowe rozwinęły system antyoksydacyjny, który skuteczne zapobiega efektom działania ROS. Przeciwutleniacze te mogą być podzielone na: enzymatyczne i nieenzymatyczne. W stanach patologicznych układ przeciwutleniaczy może być przełamany, co prowadzi do rozwoju stresu oksydacyjnego. Celem pracy jest przedstawienie podstawowych faktów dotyczących ROS i  ślinowych przeciwutleniaczy (Dent. Med. Probl. 2013, 50, 4, 461–466). Słowa kluczowe: antyoksydanty, stres oksydacyjny, wolne rodniki tlenowe.

Oxidative stress is caused by an imbalance between highly reactive molecules, such as reactive oxygen species (ROS), and the impaired function of the antioxidant body’s defense system (AOS).

This frequent pathophysiological process occurs when there are high concentrations and/or inadequate removal of ROS. Importantly, reactive oxygen species operate at an extremely rapid rate when

462 the compromised enzymatic and non-enzymatic antioxidants status does not fulfill its function [1]. Reactive oxygen species (e.g. O2•–, •OH, H2O2) play a  pivotal role in the human body, being responsible for many essential processes, including immune defense, signal transduction, matrix remodeling, cellular senescence and cell death (apoptosis). However, on the other hand, their high activity might have important biological consequences. ROS can be considered as a significant mediator of damage to major biomolecules and cell structures. Many of these damages include e.g. proteins, membrane phospholipids and nucleic acids, which are especially susceptible to oxidation by ROS [1]. As a result, chemically active intermediates and/or toxic oxidation products formed in these reactions induce cytostatic effects on cells and tissues, and consequently modulate cell metabolism and gene expression. Therefore, oxidative injury, through altered cellular homeostasis, participates in mutagenesis and carcinogenesis, and also accumulates over time. It is well documented that oxidative stress takes part in a growing number of pathological states and diseases, especially when inflammation is prominent. The purpose of this mini-review is to introduce the important findings concerning the ROS and salivary antioxidants.

Reactive Oxygen Species (ROS) Free radicals are defined in general as chemical species having one or more unpaired electrons in the outer orbit of their atoms [2]. Most of them are oxygen-containing active molecules, typically characterized by a highly short half-life. Atoms or molecules produced by the reduction of oxygen are termed reactive oxygen species (ROS). They can be divided into the following: free radicals (superoxide anion (O2•–), hydroxyl radical (•OH), and nonradical, such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) [3]. When dioxygen (O2) accepts an electron, the superoxide anion (O2•–) is generated. It represents a “primary” form of ROS and is normally produced by phagocytes during the oxidative burst triggered during inflammatory response. O2•– can directly or indirectly (e.g. enzymatic, metal catalyzed) interact with other cellular constituents to form “secondary” ROS, including peroxyl radical (ROO•) and hydrogen peroxide (H2O2)  [4–6]. For example, superoxide anion, together with metalloenzymes called superoxide dismutases (SOD), can participate in the dismutation reaction (2O2•– + 2H+ → H2O2 + O2) to produce H2O2 [7]. Finally, it should be recalled that reactive

M. Knaś et al.

nonradical species can act as oxidizing factors, and also may be transformed into radicals [8]. Additionally, there is a  distinct group of nitrogen-containing free radicals, which are named reactive nitrogen species (RNS), e.g. nitric oxide (•NO), nitrogen dioxide (•NO2) or peroxynitrite (ONOO–) [6, 9]. Nitric oxide, also known as an endothelium-derived relaxing factor (EDRF), plays an important signaling function in several biological processes, such as neurotransmission, immune responses, smooth muscle relaxation, as well as takes part in the local regulation of vascular tone and vascular architecture. Generally, •NO is formed in variety of cell types and tissues by endothelial enzyme nitric oxide synthase (NOS), which metabolise L-arginine to L-citrulline [6, 9]. Overproduction of RNS induces nitrosative stress, which can lead to nitrosylation reactions altering the structure of cellular enzymes [6, 9]. In living organisms, ROS are formed either endogenously or exogenously, and thus exposure to them is inevitable. Reactive oxygen species are typical byproducts of normal endogenous cellular metabolism; however, other sources are also possible  [7, 9]. The internal factors of ROS contain oxidative phosphorylation within mitochondria, cytochrome P450 metabolism, peroxisomal reactions, as well as a  wide range of cell enzymes, such as NADPH oxidases, lipoxygenases (LOX), cyclo-oxygenases (COX), and myeloperoxidase from activated phagocytes, especially neutrophils and macrophages [2, 6, 9, 10]. The formation of ROS occurs mostly as a  result of oxygen metabolism during mitochondrial electron transport chain (ETC) in the cell [7]. In aerobic organisms, molecular oxygen (O2) is necessary for survival, serving as an electron acceptor in numerous enzymatic and non-enzymatic processes. In this respiratory process, ATP is generated by the mitochondria-catalyzed reactions of oxygen with hydrogen in oxidative phosphorylation pathway. It is one of the major sources of energy to the body and consequently is indispensable for life. Even under normal physiological circumstances, 1–3% of all electrons are lost during transport, leading to the generation of potentially harmful oxygen free radicals  [11]. Moreover, the level of mitochondrial ROS production may change according to the cell’s physio-pathological conditions [7]. The exogenous ROS-generating processes include ionizing and non-ionizing irradiation, xenobiotics, chemical oxidants, invasion of pathogenic microorganisms (bacteria and viruses), as well as various other mechanisms. Previous studies have shown that these agents can also indirectly increase the rate of endogenous ROS generation. Exposure to ionizing radiation is known to cause

463

Oxidative Stress and Salivary Antioxidants

deleterious biological effects and can bring about DNA injury, gene mutation and cancer, most of which are mediated by ROS [12]. The production of ROS is associated with the participation of redox-active metals, and thus, reactive oxygen species can be a  product of metal-catalyzed reactions. The iron may take part in the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH−), producing very reactive and damaging hydroxyl radical  [2]. •OH has a very short half-life of approx. 10 –9 s, and thus when formed in vivo, it has the ability to react with all adjacent molecules near the site of its generation. Secondarily, hydroxyl radical may induce secretion of inflammatory cytokines, oxidize enzymes (inhibiting functional properties) and can also cause mutations in the DNA (damaging both the purine or pyrimidine bases as well as the deoxyribose backbone) [2, 10]. It should be noted that hydroxyl radical is regarded as a primary ROS which interacts with the DNA [12]. Finally, •OH is capable of initiating lipid peroxidation to produce lipid peroxyl radicals and lipid hydroperoxides, resulting in damage to the structure and fluidity of the cell membranes. According to the environment, radicals and other ROS are able to play a  double role in eukaryotic cells  [2, 6, 10]. Although for a  long time they were considered only injurious, we currently know that oxygen free radicals form an integral part of a  cell’s oxygen metabolism. Accumulating data suggest that, in low concentrations, ROS play a key role in an array of physiological processes that are crucial for cellular homeostasis. ROS along with reactive nitrogen species (RNS) may be regarded as significant signaling molecules in various enzymatic or gene-depended pathways and cellular networks, including energy metabolism, redox homeostasis, fertilization, ion channel regulation, matrix remodeling, immune responses and also apoptotic cell death [2, 6, 10, 13]. They are involved in activating and mediating hydrolysis, etherification, and phosphorylation, taking place by means of ionic mechanisms. It is well documented that reactive oxygen species promote some signal transduction cascades, such as cell proliferation-related genes (c-srk, MAPK, and Akt genes), protein phosphatases and protein kinases, for optimal activity. On the other hand, ROS and other oxidants own a large oxidizing capacity, which may be involved in oxidative stress injury. It has been proven that overproduction of ROS could have pathological consequences and directly or indirectly induce a cellular redox imbalance, leading to permanent changes in signal transduction and gene expression [9, 10, 14]. For example, ROS are able to modify the production of second messengers such as diacylglycerol and phosphatid-

ic acid (PA) [4]. Furthermore, inter alia, due to the presence of unpaired electron(s), oxygen free radicals are known to react with other biomolecules, including amino acids in proteins, polyunsaturated fatty acids (PUFA) in cell membranes and carbohydrates within DNA, inhibiting their normal functions [2]. Oxidative damage to proteins is particularly important for living systems and it is associated with the impaired cellular metabolism. In most cases, these injuries can modify the activity of cellular enzymes as well as disrupt ion homeostasis, the functioning of the receptor proteins and gap junctions that are crucial for the proper cells function [12]. It is also believed that oxidative injury induced by ROS can be the main factor of the mutation load in eukaryotic cells. A high amount of ROS can indeed modulate the intracellular redox status of the cell, thereby altering gene regulation, which can cause mutagenic effects, in particular at the tumor promotion stage of carcinogenesis [12].

Antioxidants in the Saliva The human saliva is equipped with a  variety of antioxidants that serve to counterbalance the effect of oxidants. It was reported that the major source of salivary antioxidants in humans [15] and rats [16] is parotid saliva. Antioxidants present in the saliva can be divided into the following: enzymatic and non-enzymatic.

Superoxide Dismutases One of the major enzymatic antioxidants are superoxide dismutases (SODs). These enzymes are represented in saliva by copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and extracellular superoxide dismutase (SOD3). Superoxide dismutase family catalysts dismutation reaction of superoxide anion into hydrogen peroxide and molecular oxygen (Fig. 1). Superoxide anion in the presence of superoxide dismutase is unstable [17–19]. In this case, there is a spontaneous dismutation. Salivary SOD1 is plasma born. It consists of two identical subunits, each of these contain one atom of cooper and zinc. This protein is termostable and resistant to proteolytic enzymes. SOD2 is mainly contained in the mitochondrial matrix as well as in the extracellular space and peroxisomes [20]. SOD3 is present in the extracellular space. SOD3 is a glycosylated protein with a molecular weight of 135 kDa. It is a hydrophobic enzyme, present in the form of di- and tet-

464

M. Knaś et al.

Fig. 1. Dismutation reaction of superoxide anion catalysts by superoxide dismutase family Ryc. 1. Reakcja dysmutacji anionu ponadtlenkowego katalizowana przez rodzinę enzymów dysmutaz ponadtlenkowych

rameric. SOD3 also shows properties of peroxidase. An important function of SOD3 is to protect the biological activity of nitric oxide (NO). By dismutation of superoxide anion SOD3 prevents the formation of superoxide nitrate ion [20].

Catalase Catalase is located in the peroxisomes, mitochondria, endoplasmic reticulum and cytosol. CAT is a  protein with a  molecular weight of 225 kDa and exists as a tetramer composed of four monomers, each including a heme group at the active site [21, 22]. H2O2 that is produced by SOD activity is reduced to water by catalase (Fig.  1). It should be mentioned that catalase has an affinity only to free H2O2 molecules. Catalase also binds NADPH to prevent oxidative inactivation of the enzyme by hydrogen peroxide as it is reduced to water [3]. At low concentrations of H2O2 and in vivo, catalase exhibits peroxidase-like properties, at high concentrations of H2O2 it exhibits catalaselike properties [3, 19, 23, 24].

Peroxidase Salivary peroxidase is one of the most important antioxidants synthesized by the salivary glands  [25], which oxidizes substrates, e.g. SCN-and glutathione-SH, with displaceable electrons [26]. These electrons reduce oxygen in an oxidation state –1 (H2O2) to the oxygen in the oxidation state –2 (H2O)  [27]. The name of peroxidase comes from hydrogen peroxide. The salivary peroxidase system consists of peroxidase and myelo-

peroxidase, hydrogen peroxide (H2O2) and thiocyanate ion (SCN–) [26, 28]. In a healthy salivary peroxidase, activity is mainly associated with peroxidase synthesized by acinar cells of the submandibular and parotid glands. In the inflammation of the oral cavity, myeloperoxidase, synthesized by monocytes and neutrophils, was advantageous [26, 29]. But it is absent in macrophages. Peroxidase and myeloperoxidase catalyze the oxidation of SCN–, Br– and I–. Moreover, myeloperoxidase catalyzes the oxidation of Cl– ions [30]. Moreover, peroxidase as well as mieloperoxidase catalyze the oxidation of organic compounds, such as polycyclic aromatic hydrocarbons and phenols [30].

Non-Enzymatic Antioxidants Saliva is also rich in non-enzymatic antioxidants such as ascorbic acid, albumin, glutathione, lactoferrin, vitamins and uric acid, which is the main representative agent of this group. Correlation between the level of uric acid in the saliva and plasma suggests that uric acid is plasma born [15]. It was reported that uric acid accounts for more than 85% of the total antioxidant capacity of the human unstimulated and stimulated saliva  [26]. Uric acid can act as a prooxidant, especially when it occurs in higher concentration [16]. It can also act as an antioxidant [31]. While discussing the salivary antioxidants systems, we cannot fail to mention the so-called salivary total antioxidant capacity (status) (TAC/ TAS). TAS is the sum of all antioxidants present in the saliva [26]. TAS determination has been introduced due to the fact that measuring each anti-

Oxidative Stress and Salivary Antioxidants

oxidant separately is very difficult and expensive, especially in daily clinical practice. Oxidative stress is a result of ROS overproduction by metabolic reactions that use molecular oxygen and an imbalance between oxidants and antioxidants in favor of the oxidants. We have tried to introduce the current peer-reviewed literature

465 about the nature and characteristics of free oxygen species, oxidants and the main salivary antioxidants. It should be also mentioned that in the last years, several analytical assays have been developed for measure the antioxidant activity of saliva, which indicate an increasing interest of scientists and practitioners.

References   [1] Betteridge D.J.: What is oxidative stress? Metabolism 2000, 49 (2 suppl. 1), 3–8.   [2] Rahman K.: Studies on free radicals, antioxidants, and co-factors. Clin. Interv. Aging. 2007, 2, 219–236.   [3] Birben E., Sahiner U.M., Sackesen C., Erzurum S., Kalayci O.: Oxidative stress and antioxidant defense. World Allergy Organ. J. 2012, 5, 9–19.   [4] Gaté L., Paul J., Ba G.N., Tew K.D., Tapiero H.: Oxidative stress induced in pathologies: the role of antioxidants. Biomed. Pharmacother. 1999, 53, 169–180.   [5] Tremellen K.: Oxidative stress and male infertility – a clinical perspective. Hum. Reprod. Update 2008, 14, 243–258.   [6] Valko M., Rhodes C.J., Moncol J., Izakovic M., Mazur M.: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 2006, 160, 1–40.   [7] Venditti P., Di Stefano L., Di Meo S.: Mitochondrial metabolism of reactive oxygen species. Mitochondrion. 2013, 13, 71–82.   [8] Goodyear-Bruch C., Pierce J.D.: Oxidative stress in critically Ill patients. Am. J. Crit. Care 2002, 11, 543–551.   [9] Kimura H., Sawada T., Oshima S., Kozawa K., Ishioka T., Kato M.: Toxicity and roles of reactive oxygen species. Curr. Drug. Targets. Inflamm. Allergy 2005, 4, 489–495. [10] Valko M., Leibfritz D., Moncol J., Cronin M.T.D., Mazur M., Telser J.: Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell. Biol. 2007, 39, 44–84. [11] Podda M., Grundmann-Kollmann M.: Low molecular weight antioxidants and their role in skin ageing. Clin. Exp. Dermatol. 2001, 26, 578–582. [12] Klaunig J.E., Wang Z., Pu X., Zhou S.: Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol. Appl. Pharmacol. 2011, 254, 86–99. [13] Becker L.B.: New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc. Res. 2004, 61, 461–470. [14] Afanas’ev I.: Signaling by reactive oxygen and nitrogen species in skin diseases. Curr. Drug. Metab. 2010, 11, 409–414. [15] Nagler R.M., Klein I., Zarzhevsky N., Drigues N., Reznick A.Z.: Characterization of the differentiated antioxidant profile of human saliva. Free Radic. Biol. Med. 2002, 32, 268–277. [16] Zalewska A., Knaś M., Żendzian-Piotrowska M., Waszkiewicz N., Szulimowska J., Prokopiuk S., Waszkiel D., Car H.: Antioxidant profile of salivary glands in high fat diet-induced insulin resistance rats. Oral. Dis. 2013, doi.: 10.1111/odi.12173, [Epub ahead of print]. [17] Kulbacka J., Saczko J., Chwiłkowska A.: Oxidative stress in cells damage processes. Pol. Merk. Lek. 2009, 27, 44–47 [in Polish]. [18] Łagowska-Lenard M., Bielewicz J., Raszewski G., Stelmasiak Z., Bartosik-Psujek H.: Oxidative stress in stroke. Pol. Merk. Lek. 2008, 25, 205–208 [in Polish]. [19] Ostrowska J., Makieła M., Zwierz K.: Contribution of oxidative stress in liver injury. Hepatologia 2004, 4, 28–32 [in Polish]. [20] Frederiks W.M., Bosch K.S.: Localization of superoxide dismutase activity in rat tissues. Free Radic. Biol. Med. 1997, 22, 241–248. [21] Ceriello A.: Oxidative stress and glycemic regulation. Metabolism 2000, 49 (2 suppl. 1), 27–29. [22] Parihar A., Parihar M.S., Milner S., Bhat S.: Oxidative stress and anti-oxidative mobilization in burn injury. Burns 2008, 34, 6–17. [23] Michiels C., Raes M., Toussaint O., Remacle J.: Importance of Se-glutathione peroxidase, catalase, and Cu/ZnSOD for cell survival against oxidative stress. Free Radic. Biol. Med. 1994, 17, 235–248. [24] Putnam C.D., Arvai A.S., Bourne Y., Tainer J.A.: Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. J. Mol. Biol. 2000, 296, 295–309. [25] Waszkiewicz N., Zalewska A., Szajda S.D., Szulc A., Kępka A., Minarowska A., Wojewódzka-Żelezniakowicz M., Konarzewska B., Chojnowska S., Supronowicz Z.B., Ładny J.R., Zwierz K.: The effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase. Folia Histochem. Cytobiol. 2012, 50, 450–455. [26] Battino M., Ferreivo M.S., Gallardo I., Newman H.N., Bullon P.: The antioxidant capacity of saliva. J. Clin. Periodontol. 2002, 29, 189–194. [27] Bolesta D., Hościowicz P.D., Knaś M., Waszkiel D., Zalewska A.: Diabetes mellitus-related oxidative stress and its parameters in saliva. Pol. Merk. Lek. 2013, 209, 300–305. [28] Kanehira T., Shibata K., Kashiwazaki H., Inoue N., Morita M.: Comparison of antioxidant enzymes in saliva of eldery smokers and non-smokers. Gerodontology 2006, 23, 38–42. [29] Gorr S.U.: Antimicrobial peptides of the oral cavity. Periodontology 2009, 51, 152–180.

466

M. Knaś et al.

[30] Tenovuo J., Pruiti K.M.: Relationship of the human salivary peroxidase system to oral health. J. Oral. Pathol. 1984, 13, 573–584. [31] Zalewska A., Knaś M., Waszkiewicz N., Klimiuk A., Litwin K., Sierakowski S., Waszkiel D.: Salivary antioxidants in patients with systemic sclerosis. J. Oral. Pathol. Med. 2013, doi.: 10.1111/jop.12084, [Epub ahead of print].

Address for correspondence: Małgorzata Knaś Noniewicza 10 Str. 16-400 Suwałki Poland Tel.: 600 549 562 E-mail: [email protected] Received: 26.11.2013 Revised: 13.12.2013 Accepted: 17.12.2013 Praca wpłynęła do Redakcji: 26.11.2013 r. Po recenzji: 13.12.2013 r. Zaakceptowano do druku: 17.12.2013 r.