Inflammation is a part of the complex biological response of vascular tissues to harmful stimuli. Debilitating diseases such as atherosclerosis, rheumatoid arthritis, and even cancer are the biggest pharmacological hurdles of today. Targeting inflammation is a broad task, since many mediators are involved in onset of particular disease. Among these many mediators, the reactive oxygen and nitrogen species generated by macrophages and neutrophils are of great interest because of their major contribution in establishment of chronic inflammation and cancer. This review elaborates the pathogenesis of inflammation based on involvement of reactive oxygen and nitrogen species and the activation of signalling cascades in response to oxidative stress. Understanding this would eventually give a clue for target based therapeutic approach in search of new effective anti-inflammatory drugs.
References
[1]
Kanwar, J.R., Kanwar, R.K., Burrow, H. and Baratchi, S. (2009) Recent Advances on the Roles of NO in Cancer and Chronic Inflammatory Disorders. Current Medicinal Chemistry, 16, 2373-2394. https://doi.org/10.2174/092986709788682155
[2]
Kumar, S., Bajwa, B.S., Kuldeep, S. and Kalia, A.N. (2013) Anti-Inflammatory Activity of Herbal Plants: A Review. International Journal of Advances in Pharmacy, Biology and Chemistry, 2, 272-281.
[3]
Kumar, V., Abbas, A.K. and Aster, J.C. (2017) Robbins Basic Pathology. E-Book, Elsevier Health Sciences, Amsterdam, 57-97.
[4]
Fujiwara, N. and Kobayashi, K. (2005) Macrophages in Inflammation. Current Drug Targets-Inflammation and Allergy, 4, 281-286.
https://doi.org/10.2174/1568010054022024
[5]
Winrow, V.R., Winyard, P.G., Morris, C.J. and Blake, D.R. (1993) Free Radicals in Inflammation: Second Messengers and Mediators of Tissue Destruction. British Medical Bulletin, 49, 506-522. https://doi.org/10.1093/oxfordjournals.bmb.a072627
[6]
Matés, J.M. and Sánchez-Jiménez, F. (1999) Antioxidant Enzymes and Their Implications in Pathophysiologic Processes. Frontiers in Bioscience, 4, 339-345.
https://doi.org/10.2741/A432
[7]
Chapple, I.L.C. (1997) Reactive Oxygen Species and Antioxidants in Inflammatory Diseases. Journal of Clinical Periodontology, 24, 287-296.
https://doi.org/10.1111/j.1600-051X.1997.tb00760.x
[8]
Maier, C.M. and Chan, P.H. (2002) Book Review: Role of Superoxide Dismutases in Oxidative Damage and Neurodegenerative Disorders. The Neuroscientist, 8, 323-334. https://doi.org/10.1177/107385840200800408
[9]
Rahman, I., Marwick, J. and Kirkham, P. (2004) Redox Modulation of Chromatin Remodeling: Impact on Histone Acetylation and Deacetylation, NF-κB and Pro-Inflammatory Gene Expression. Biochemical Pharmacology, 68, 1255-1267.
https://doi.org/10.1016/j.bcp.2004.05.042
[10]
Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T., Mazur, M. and Telser, J. (2007) Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. The International Journal of Biochemistry and Cell Biology, 39, 44-84.
https://doi.org/10.1016/j.biocel.2006.07.001
[11]
Wira, C.R., Fahey, J.V., Sentman, C.L., Pioli, P.A. and Shen, L. (2005) Innate and Adaptive Immunity in Female Genital Tract: Cellular Responses and Interactions. Immunological Reviews, 206, 306-335.
https://doi.org/10.1111/j.0105-2896.2005.00287.x
[12]
Hanisch, U.K. (2002) Microglia as a Source and Target of Cytokines. Glia, 40, 140-155. https://doi.org/10.1002/glia.10161
[13]
Gasque, P., Singhrao, S.K., Neal, J.W., Wang, P., Sayah, S., Fontaine, M. and Morgan, B.P. (1998) The Receptor for Complement Anaphylatoxin C3a Is Expressed by Myeloid Cells and Nonmyeloid Cells in Inflamed Human Central Nervous System: Analysis in Multiple Sclerosis and Bacterial Meningitis. The Journal of Immunology, 160, 3543-3554.
[14]
Nathan, C. (1992) Nitric Oxide as a Secretory Product of Mammalian Cells. The FASEB Journal, 6, 3051-3064. https://doi.org/10.1096/fasebj.6.12.1381691
[15]
Dong, H., Zhang, X. and Qian, Y. (2014) Mast Cells and Neuroinflammation. Medical Science Monitor Basic Research, 20, 200-206.
https://doi.org/10.12659/MSMBR.893093
[16]
Mollace, V., Muscoli, C., Masini, E., Cuzzocrea, S. and Salvemini, D. (2005) Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors. Pharmacological Reviews, 57, 217-252. https://doi.org/10.1124/pr.57.2.1
[17]
Wu, J., Rutkowski, D.T., Dubois, M., Swathirajan, J., Saunders, T., Wang, J. and Kaufman, R.J. (2007) ATF6α Optimizes Long-Term Endoplasmic Reticulum Function to Protect Cells from Chronic Stress. Developmental Cell, 13, 351-364.
https://doi.org/10.1016/j.devcel.2007.07.005
[18]
Almeida, J.R.G.D.S., Souza, G.R., Silva, J.C., Saraiva, S.R.G.D.L., Júnior, R.G.D.O., Quintans, J.D.S.S. and Junior, L.J.Q. (2013) Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice. The Scientific World Journal, 2013, Article ID: 808460.
[19]
Netea, M.G., Kullberg, B.J. and Van Der Meer, J.W. (2000) Circulating Cytokines as Mediators of Fever. Clinical Infectious Diseases, 31, S178-S184.
https://doi.org/10.1086/317513
[20]
Edwards, S.W. (2005) Biochemistry and Physiology of the Neutrophil. Cambridge University Press, Cambridge.
[21]
Valko, M., Rhodes, C., Moncol, J., Izakovic, M.M. and Mazur, M. (2006) Free Radicals, Metals and Antioxidants in Oxidative Stress-Induced Cancer. Chemico-Biological Interactions, 160, 1-40. https://doi.org/10.1016/j.cbi.2005.12.009
[22]
Wojtaszek, P. (1997) Oxidative Burst: An Early Plant Response to Pathogen Infection. Biochemical Journal, 322, 681-692. https://doi.org/10.1042/bj3220681
[23]
Badwey, J.A. and Karnovsky, M.L. (1980) Active Oxygen Species and the Functions of Phagocytic Leukocytes. Annual Review of Biochemistry, 49, 695-726.
https://doi.org/10.1146/annurev.bi.49.070180.003403
[24]
Babior, B.M. (2000) Phagocytes and Oxidative Stress. The American Journal of Medicine, 109, 33-44. https://doi.org/10.1016/S0002-9343(00)00481-2
[25]
Heyneman, R.A. and Vercauteren, R.E. (1984) Activation of a NADPH Oxidase from Horse Polymorphonuclear Leukocytes in a Cell-Free System. Journal of Leukocyte Biology, 36, 751-759. https://doi.org/10.1002/jlb.36.6.751
[26]
Dedon, P.C. and Tannenbaum, S.R. (2004) Reactive Nitrogen Species in the Chemical Biology of Inflammation. Archives of Biochemistry and Biophysics, 423, 12-22.
https://doi.org/10.1016/j.abb.2003.12.017
[27]
Schottenfeld, D. and Beebe-Dimmer, J. (2006) Chronic Inflammation: A Common and Important Factor in the Pathogenesis of Neoplasia. CA: A Cancer Journal for Clinicians, 56, 69-83. https://doi.org/10.3322/canjclin.56.2.69
[28]
Roussos, A., Philippou, N. and Gourgoulianis, K.I. (2003) Helicobacter pylori Infection and Respiratory Diseases: A Review. World Journal of Gastroenterology, 9, 5-8.
https://doi.org/10.3748/wjg.v9.i1.5
[29]
Gencer, M., Ceylan, E., Zeyrek, F.Y. and Aksoy, N. (2007) Helicobacter pylori Seroprevalence in Patients with Chronic Obstructive Pulmonary Disease and Its Relation to Pulmonary Function Tests. Respiration, 74, 170-175.
https://doi.org/10.1159/000090158
[30]
Jaiswal, M., LaRusso, N.F. and Gores, G.J. (2001) Nitric Oxide in Gastrointestinal Epithelial Cell Carcinogenesis: Linking Inflammation to Oncogenesis. American Journal of Physiology—Gastrointestinal and Liver Physiology, 281, G626-G634.
https://doi.org/10.1152/ajpgi.2001.281.3.G626
[31]
Kelly, R.A., Balligand, J.L. and Smith, T.W. (1996) Nitric Oxide and Cardiac Function. Circulation Research, 79, 363-380. https://doi.org/10.1161/01.RES.79.3.363
[32]
Asano, K., Chee, C.B., Gaston, B., Lilly, C.M., Gerard, C., Drazen, J.M. and Stamler, J.S. (1994) Constitutive and Inducible Nitric Oxide Synthase Gene Expression, Regulation, and Activity in Human Lung Epithelial Cells. Proceedings of the National Academy of Sciences of the United States of America, 91, 10089-10093.
https://doi.org/10.1073/pnas.91.21.10089
[33]
Pannu, R. and Singh, I. (2006) Pharmacological Strategies for the Regulation of Inducible Nitric Oxide Synthase: Neurodegenerative versus Neuroprotective Mechanisms. Neurochemistry International, 49, 170-182.
https://doi.org/10.1016/j.neuint.2006.04.010
[34]
Abu-Soud, H.M., Loftus, M. and Stuehr, D.J. (1995) Subunit Dissociation and Unfolding of Macrophage NO Synthase: Relationship between Enzyme Structure, Prosthetic Group Binding, and Catalytic Function. Biochemistry, 34, 11167-11175.
https://doi.org/10.1021/bi00035a023
[35]
Moncada, S. and Higgs, E.A. (1995) Molecular Mechanisms and Therapeutic Strategies Related to Nitric Oxide. The FASEB Journal, 9, 1319-1330.
https://doi.org/10.1096/fasebj.9.13.7557022
[36]
Venema, R.C., Sayegh, H.S., Kent, J.D. and Harrison, D.G. (1996) Identification, Characterization, and Comparison of the Calmodulin-Binding Domains of the Endothelial and Inducible Nitric Oxide Synthases. Journal of Biological Chemistry, 271, 6435-6440. https://doi.org/10.1074/jbc.271.11.6435
[37]
Cai, S., Khoo, J., Mussa, S., Alp, N.J. and Channon, K.M. (2005) Endothelial Nitric Oxide Synthase Dysfunction in Diabetic Mice: Importance of Tetrahydrobiopterin in eNOS Dimerisation. Diabetologia, 48, 1933-1940.
https://doi.org/10.1007/s00125-005-1857-5
[38]
Medzhitov, R. (2001) Toll-Like Receptors and Innate Immunity. Nature Reviews Immunology, 1, 135. https://doi.org/10.1038/35100529
[39]
Anderson, K.V. (2000) Toll Signaling Pathways in the Innate Immune Response. Current Opinion in Immunology, 12, 13-19.
https://doi.org/10.1016/S0952-7915(99)00045-X
[40]
Wendehenne, D., Pugin, A., Klessig, D.F. and Durner, J. (2001) Nitric Oxide: Comparative Synthesis and Signaling in Animal and Plant Cells. Trends in Plant Science, 6, 177-183. https://doi.org/10.1016/S1360-1385(01)01893-3
[41]
Klessig, D.F., Durner, J., Noad, R., Navarre, D.A., Wendehenne, D., Kumar, D. and Trifa, Y. (2000) Nitric Oxide and Salicylic Acid Signaling in Plant Defense. Proceedings of the National Academy of Sciences of the United States of America, 97, 8849-8855. https://doi.org/10.1073/pnas.97.16.8849
[42]
Garthwaite, J. and Boulton, C.L. (1995) Nitric Oxide Signaling in the Central Nervous System. Annual Review of Physiology, 57, 683-706.
https://doi.org/10.1146/annurev.ph.57.030195.003343
[43]
Dauphinee, S.M. and Karsan, A. (2006) Lipopolysaccharide Signaling in Endothelial Cells. Laboratory Investigation, 86, 9-22. https://doi.org/10.1038/labinvest.3700366
[44]
Aktan, F. (2004) iNOS-Mediated Nitric Oxide Production and Its Regulation. Life Sciences, 75, 639-653. https://doi.org/10.1016/j.lfs.2003.10.042
[45]
Schroder, K., Hertzog, P.J., Ravasi, T. and Hume, D.A. (2004) Interferon-γ: An Overview of Signals, Mechanisms and Functions. Journal of Leukocyte Biology, 75, 163-189. https://doi.org/10.1189/jlb.0603252
[46]
Grossmann, M., Nakamura, Y., Grumont, R. and Gerondakis, S. (1999) New Insights into the Roles of ReL/NF-κB Transcription Factors in Immune Function, Hemopoiesis and Human Disease. The International Journal of Biochemistry and Cell Biology, 31, 1209-1219. https://doi.org/10.1016/S1357-2725(99)00068-0
[47]
Taniguchi, T. and Takaoka, A. (2001) A Weak Signal for Strong Responses: Interferon-Alpha/Beta Revisited. Nature Reviews Molecular Cell Biology, 2, 378-386.
https://doi.org/10.1038/35073080
[48]
López-Franco, O., Suzuki, Y., Sanjuán, G., Blanco, J., Hernández-Vargas, P., Yo, Y. and Gómez-Guerrero, C. (2002) Nuclear Factor-κB Inhibitors as Potential Novel Anti-Inflammatory Agents for the Treatment of Immune Glomerulonephritis. The American Journal of Pathology, 161, 1497-1505.
https://doi.org/10.1016/S0002-9440(10)64425-2
[49]
Qin, L., Liu, Y., Wang, T., Wei, S.J., Block, M.L., Wilson, B. and Hong, J.S. (2004) NADPH Oxidase Mediates Lipopolysaccharide-Induced Neurotoxicity and Proinflammatory Gene Expression in Activated Microglia. Journal of Biological Chemistry, 279, 1415-1421. https://doi.org/10.1074/jbc.M307657200
[50]
Kar, S. and Kavdia, M. (2012) Impact of SOD on Endothelial Cell Free Radical Distribution during eNOS Uncoupling. The FASEB Journal, 26, 1098.
[51]
Meissner, F., Seger, R.A., Moshous, D., Fischer, A., Reichenbach, J. and Zychlinsky, A. (2010) Inflammasome Activation in NADPH Oxidase Defective Mononuclear Phagocytes from Patients with Chronic Granulomatous Disease. Blood, 116, 1570-1573. https://doi.org/10.1182/blood-2010-01-264218
[52]
Lambertucci, R.H., Hirabara, S.M., Silveira, L.D.R., Levada-Pires, A.C., Curi, R. and Pithon-Curi, T.C. (2008) Palmitate Increases Superoxide Production through Mitochondrial Electron Transport Chain and NADPH Oxidase Activity in Skeletal Muscle Cells. Journal of Cellular Physiology, 216, 796-804.
https://doi.org/10.1002/jcp.21463
[53]
Hamanaka, R.B. and Chandel, N.S. (2009) Mitochondrial Reactive Oxygen Species Regulate Hypoxic Signaling. Current Opinion in Cell Biology, 21, 894-899.
https://doi.org/10.1016/j.ceb.2009.08.005
[54]
Bokoch, G.M. and Diebold, B.A. (2002) Current Molecular Models for NADPH Oxidase Regulation by Rac GTPase. Blood, 100, 2692-2695.
https://doi.org/10.1182/blood-2002-04-1149
[55]
Frey, R.S., Ushio-Fukai, M. and Malik, A.B. (2009) NADPH Oxidase-Dependent Signaling in Endothelial Cells: Role in Physiology and Pathophysiology. Antioxidants and Redox Signaling, 11, 791-810. https://doi.org/10.1089/ars.2008.2220
[56]
Groemping, Y. and Rittinger, K. (2005) Activation and Assembly of the NADPH Oxidase: A Structural Perspective. Biochemical Journal, 386, 401-416.
https://doi.org/10.1042/BJ20041835
[57]
De Leo, F.R. and Quinn, M.T. (1996) Assembly of the Phagocyte NADPH Oxidase: Molecular Interaction of Oxidase Proteins. Journal of Leukocyte Biology, 60, 677-691. https://doi.org/10.1002/jlb.60.6.677
[58]
Babior, B.M. (1999) NADPH Oxidase: An Update. Blood, 93, 1464-1476.
[59]
Elbim, C. (2005) Phagocyte NADPH Oxidase: A Multicomponent Enzyme Essential for Host Defenses. Archivum Immunologiae et Therapiae Experimentalis, 53, 199-206.
[60]
Franck, T., Kohnen, S., De la Rebière, G., Deby-Dupont, G., Deby, C., Niesten, A. and Serteyn, D. (2009) Activation of Equine Neutrophils by Phorbol Myristate Acetate or N-Formyl-Methionyl-Leucyl-Phenylalanine Induces a Different Response in Reactive Oxygen Species Production and Release of Active Myeloperoxidase. Veterinary Immunology and Immunopathology, 130, 243-250.
https://doi.org/10.1016/j.vetimm.2009.02.015
[61]
Jones, G.E., Allen, W.E. and Ridley, A.J. (1998) The Rho GTPases in Macrophage Motility and Chemotaxis. Cell Adhesion and Communication, 6, 237-245.
https://doi.org/10.3109/15419069809004479
[62]
Hackam, D.J., Rotstein, O.D., Schreiber, A., Zhang, W.J. and Grinstein, S. (1997) Rho Is Required for the Initiation of Calcium Signaling and Phagocytosis by Fcγ Receptors in Macrophages. Journal of Experimental Medicine, 186, 955-966.
https://doi.org/10.1084/jem.186.6.955
[63]
Bosch, E., Horwitz, J. and Bok, D. (1993) Phagocytosis of Outer Segments by Retinal Pigment Epithelium: Phagosome-Lysosome Interaction. Journal of Histochemistryand Cytochemistry, 41, 253-263. https://doi.org/10.1177/41.2.8419462
[64]
Mercado, C. and Jaimes, E.A. (2007) Cigarette Smoking as a Risk Factor for Atherosclerosis and Renal Disease: Novel Pathogenic Insights. Current Hypertension Reports, 9, 66-72. https://doi.org/10.1007/s11906-007-0012-8
[65]
McCormick, M.L., Gavrila, D. and Weintraub, N.L. (2007) Role of Oxidative Stress in the Pathogenesis of Abdominal Aortic Aneurysms. Arteriosclerosis, Thrombosis, and Vascular Biology, 27, 461-469.
https://doi.org/10.1161/01.ATV.0000257552.94483.14
[66]
Ignarro, L. (2005) No More Heart Disease: How Nitric Oxide Can Prevent—Even Reverse—Heart Disease and Strokes. St. Martin’s Griffin, Macmillan.
[67]
Wallace, J.L., Ignarro, L.J. and Fiorucci, S. (2002) Potential Cardioprotective Actions of No-Releasing Aspirin. Nature Reviews Drug Discovery, 1, 375-382.
https://doi.org/10.1038/nrd794
[68]
Chatterjee, A. and Catravas, J.D. (2008) Endothelial Nitric Oxide (NO) and Its Pathophysiologic Regulation. Vascular Pharmacology, 49, 134-140.
https://doi.org/10.1016/j.vph.2008.06.008
[69]
Ding, W., Hudson, L.G. and Liu, K.J. (2005) Inorganic Arsenic Compounds Cause Oxidative Damage to DNA and Protein by Inducing ROS and RNS Generation in Human Keratinocytes. Molecular and Cellular Biochemistry, 279, 105-112.
https://doi.org/10.1007/s11010-005-8227-y
[70]
Svobodova, A., Walterova, D. and Vostalova, J. (2006) Ultraviolet Light Induced Alteration to the Skin. Biomedical Papers-Palacky University in Olomouc, 150, 25-38. https://doi.org/10.5507/bp.2006.003
[71]
Choudhari, S.K., Chaudhary, M., Gadbail, A.R., Sharma, A. and Tekade, S. (2014) Oxidative and Antioxidative Mechanisms in Oral Cancer and Precancer: A Review. Oral Oncology, 50, 10-18. https://doi.org/10.1016/j.oraloncology.2013.09.011
[72]
Murakami, A. and Ohigashi, H. (2007) Targeting NOX, INOS and COX-2 in Inflammatory Cells: Chemoprevention Using Food Phytochemicals. International Journal of Cancer, 121, 2357-2363. https://doi.org/10.1002/ijc.23161
[73]
Hall, D.T., Ma, J.F., Di Marco, S. and Gallouzi, I.E. (2011) Inducible Nitric Oxide Synthase (iNOS) in Muscle Wasting Syndrome, Sarcopenia, and Cachexia. Aging (Albany NY), 3, 702-715. https://doi.org/10.18632/aging.100358
[74]
Murakami, A. (2009) Chemoprevention with Phytochemicals Targeting Inducible Nitric Oxide Synthase. In: Yoshikawa, T., Ed., Food Factors for Health Promotion, Vol. 61, Karger Publishers, Basel, Switzerland, 193-203.
https://doi.org/10.1159/000212751
[75]
Tak, P.P. and Firestein, G.S. (2001) NF-κB: A Key Role in Inflammatory Diseases. The Journal of Clinical Investigation, 107, 7-11. https://doi.org/10.1172/JCI11830
[76]
Cave, A. (2009) Selective Targeting of NADPH Oxidase for Cardiovascular Protection. Current Opinion in Pharmacology, 9, 208-213.
https://doi.org/10.1016/j.coph.2008.10.001
[77]
Williams, H.C. and Griendling, K.K. (2007) NADPH Oxidase Inhibitors: New Antihypertensive Agents? Journal of Cardiovascular Pharmacology, 50, 9-16.
https://doi.org/10.1097/FJC.0b013e318063e820
[78]
Takeya, R., Ueno, N., Kami, K., Taura, M., Kohjima, M., Izaki, T., Nunoi, H. and Sumimoto, H. (2003) Novel Human Homologues of p47phox and p67phox Participate in Activation of Superoxide-Producing NADPH Oxidases. Journal of Biological Chemistry, 278, 25234-25246. https://doi.org/10.1074/jbc.M212856200
[79]
Streeter, J., Thiel, W., Brieger, K. and Miller Jr, F.J. (2013) Opportunity Nox: The Future of NADPH Oxidases as Therapeutic Targets in Cardiovascular Disease. Cardiovascular Therapeutics, 31, 125-137.
https://doi.org/10.1111/j.1755-5922.2011.00310.x
[80]
Rainsford, K.D. (2007) Anti-Inflammatory Drugs in the 21st Century. In: Randall, E., Harris, R., et al., Eds., Inflammation in the Pathogenesis of Chronic Diseases, Springer, Dordrecht, 3-27. https://doi.org/10.1007/1-4020-5688-5_1
[81]
Iwalewa, E.O., McGaw, L.J., Naidoo, V. and Eloff, J.N. (2007) Inflammation: The Foundation of Diseases and Disorders. A Review of Phytomedicines of South African Origin Used to Treat Pain and Inflammatory Conditions. African Journal of Biotechnology, 6, 2868-2885.
[82]
Surveswaran, S., Cai, Y.Z., Corke, H. and Sun, M. (2007) Systematic Evaluation of Natural Phenolic Antioxidants from 133 Indian Medicinal Plants. Food Chemistry, 102, 938-953. https://doi.org/10.1016/j.foodchem.2006.06.033
[83]
Shah, M.R., Arfan, M., Amin, H., Hussain, Z., Qadir, M.I., Choudhary, M.I. and Khan, I.U. (2012) Synthesis of New Bergenin Derivatives as Potent Inhibitors of Inflammatory Mediators NO and TNF-α. Bioorganic and Medicinal Chemistry Letters, 22, 2744-2747. https://doi.org/10.1016/j.bmcl.2012.02.096
[84]
Sutherland, L.R. and MacDonald, J.K. (2016) Oral 5-Aminosalicylic Acid for Maintenance of Remission in Ulcerative Colitis. Cochrane Database of Systematic Reviews, 9, Art. No. CD000544. https://doi.org/10.1002/14651858.CD000544.pub2
[85]
Ristow, M. and Schmeisser, K. (2014) Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose-Response, 12, 288-341. https://doi.org/10.2203/dose-response.13-035.Ristow
[86]
Balaban, R.S., Nemoto, S. and Finkel, T. (2005) Mitochondria, Oxidants, and Aging. Cell, 120, 483-495. https://doi.org/10.1016/j.cell.2005.02.001
[87]
Alexeyev, M.F. (2009) Is There More to Aging than Mitochondrial DNA and Reactive Oxygen Species? The FEBS Journal, 276, 5768-5787.
https://doi.org/10.1111/j.1742-4658.2009.07269.x
[88]
Poljsak, B. (2011) Strategies for Reducing or Preventing the Generation of Oxidative Stress. Oxidative Medicine and Cellular Longevity, 2011, Article ID: 194586.
https://doi.org/10.1155/2011/194586
[89]
Bloom, B.S. (1988) Cost of Treating Arthritis and NSAID-Related Gastrointestinal Side-Effects. Alimentary Pharmacology and Therapeutics, 2, 131-139.
https://doi.org/10.1111/j.1365-2036.1988.tb00772.x
[90]
Hedner, T. and Everts, B. (1998) The Early Clinical History of Salicylates in Rheumatology and Pain. Clinical Rheumatology, 17, 17-25.
https://doi.org/10.1007/BF01450953
[91]
Laine, L., Bombardier, C., Hawkey, C.J., Davis, B., Shapiro, D., Brett, C. and Reicin, A. (2002) Stratifying the Risk of NSAID-Related Upper Gastrointestinal Clinical Events: Results of a Double-Blind Outcomes Study in Patients with Rheumatoid Arthritis. Gastroenterology, 123, 1006-1012.
https://doi.org/10.1053/gast.2002.36013