Oxidative stress in rheumatoid arthritis: what the future might hold regarding novel biomarkers and add-on therapies

Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction-self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?-represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis

Growth inhibitory effects of 3′-nitro-3-phenylamino nor-beta-lapachone against HL-60: A redox-dependent mechanism

AbstractIn this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3′-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO2) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF4) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO2. QPhNO2 caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO2 treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry

Alternating Layers Of Iron(iii) Tetra(n-methyl-4-pyridyl) -porphyrin And Copper Tetrasulfonated Phthalocyanine For Amperometric Detection Of 4-nitrophenol In Nanomolar Levels

The present work describes the development of a highly sensitive amperometric sensor for 4-NP in nanomolar levels using a glassy carbon electrode modified with alternating layers of CuTSPc and FeT4MPyP. After optimizing the operational conditions, the sensor provided a linear response range for 4-NP from 5 up to 100 nmol L-1 with sensitivity, detection, and quantification limits of 14 nA L nmol-1, 1.9 nmol L-1, and 5.4 nmol L-1, respectively. The proposed sensor showed a stable response for at least 200 successive determinations. This modified electrode can be used to the determination of 4-NP in water samples. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.202123332339Nevskaia, D.M., Castillejos-Lopez, E., Munoz, V., Guerrero-Ruiz, A., (2004) Environ. Sci. Technol, 38, p. 5786Davi, M.L., Gnudi, F., (1999) Water Res, 33, p. 3213(2004) National Recommended Water Quality Criteria, , U.S. Environmental Protection Agency EPAWilliams, A.I., (1971) Analyst, 96, p. 296Frenzel, W., Frenzel, J.O., Moeller, J., (1992) Anal. Chim. Acta, 261, p. 253Realini, P.A., (1981) J. Chromatogr. Sci, 19, p. 124Berger, T.A., Deye, J.F., (1991) Chromatogr. Sci, 29, p. 54Brage, C., Sjöström, K.J., (1991) Chromatography, 538, p. 303Emerson, E., (1948) J. Org. Chem, 8, p. 417Emerson, E., Kelly, K., (1948) J. Org. Chem, 13, p. 532Ettinger, M., Ruchhoft, C., Lishka, R., (1951) Anal. Chem, 23, p. 1783Fiamegos, Y.C., Stalikas, C.D., Pilidis, G.A., Karayannis, M.I., (2000) Anal. Chim. Acta, 403, p. 315Fiamegos, Y.C., Stalikas, C.D., Pilidis, G.A., Karayannis, M.I., (1997) Anal. Chim. Acta, 356, p. 165Fiamegos, Y., Stalikas, C., Pilidis, G., (2002) Anal. Chim. Acta, 467, p. 105Luz, R.C.S., Damos, F.S., Oliveira, A.B., Beck, J., Kubota, L.T., (2004) Talanta, 64, p. 935Pedrosa, V.D., Codognoto, L., Avaca, L.A., (2003) J. Braz. Chem. Soc, 14, p. 530Nafaa, A., Monser, M.L., Toumi, K.B., (2003) Anal. Chim. Acta, 495, p. 69Ljeri, V.S., Jaiswal, P.V., Scrivastava, A.K., (2001) Anal. Chim. Acta, 439, p. 291Lima, P.R., Santos, W.J.R., Oliveira, A.B., Goulart, M.O.F., Kubota, L.T., (2008) J. Pharm. Biomed. Anal, 47, p. 758P. R. Lima, W. J. R. Santos, R. de C. S. Luz, F. S. Damos, A. B. Oliveira, M. O. F. Goulart, L. T. Kubota, J. Electroanal. Chem. 2008, 612, 87Sotomayor, M.D.P., Kubota, L.T., Tanaka, A.A., (2003) Electrochim. Acta, 48, p. 855Sotomayor, M.D.P., Kubota, L.T., Tanaka, A.A., (2002) Anal. Chim. Acta, 455, p. 215Wring, S.A., Hart, J.P., (1992) Analyst, 1215, p. 117Yang, S.M., Li, Y.M., Jiang, X.M., Chen, Z.C., Lin, X.F., (2006) Sens. Actuators B, Chem, 114, p. 774Huang, H.X., Qian, D.J., Nakamura, N., Nakamura, C., Wakayama, T., Miyake, J., (2004) Electrochim. Acta, 49, p. 1491Sun, C., Zhao, J., Xu, H., Sun, Y., Zhang, X., Shen, J., (1998) Talanta, 46, p. 15Manriquez, J., Bravo, J.L., Granados, S.G., Succar, S.S., Bied Charreton, C., Ordaz, A.A., Bedioui, F., (1999) Anal. Chim. Acta, 378, p. 159Mimica, D., Zagal, J.H., Bedioui, F., (2001) Electrochim. Commun, 3, p. 435Ozoemena, K.I., Nyokong, T., (2005) Talanta, 67, p. 162Ozoemena, K.I., Zhao, Z., Nyokong, T., (2005) Electrochem. Commun, 7, p. 679Weber, J.H., Busch, D.H., (1965) Inorg. Chem, 4, p. 469Rocha, J.R.C., Angnes, L., Bertotti, M., Araki, K., Toma, H.E., (2002) Anal. Chim. Acta, 452, p. 23Hu, S., Xu, C., Wang, G., Cui, D., (2001) Talanta, 54, p. 115de Groot, M.T., Merkx, M., Koper, M.T.M., (2007) C. R. Chimie, 10, p. 414Mayer, I., Nakamura, M., Toma, H.E., Araki, K., (2006) Electrochim. Acta, 52, p. 263Richard, J.A., Whitson, P.E., Evans, D.H., (1975) J. Electroanal. Chem, 63, p. 3111Papouchado, L., Sandford, R.W., Petrie, G., Adams, R.N., (1975) J. Electroanal. Chem, 65, p. 275Pariente, F., Lorenzo, E., Tobalina, F., Abruna, H.D., (1995) Anal. Chem, 67, p. 3936Bard, A.J., Faulkner, L.R., (2001) Electrochemical methods, Fundamentals and applications, , Wiley, New YorkNiesner, R., Heintz, A., (2000) J. Chem. Eng. Data, 45, p. 1121Yongian, N., Wang, L., Serge, K., (2001) Anal. Chim. Acta, 431, p. 101Rocha, J.R.C., Demets, G.J.-F., Bertotti, M., Araki, K., Toma, H.E., (2002) J. Electroanal. Chem, 526, p. 69Beissenhirtz, M.K., Scheller, F.W., Lisdat, F., (2004) Anal. Chem, 76, p. 4665Rocha, J.R.C., Angnes, L., Bertotti, M., Araki, K., Toma, H.E., (2002) Anal. Chim. Acta, 452, p. 23(1987) Analyst, 112, p. 199. , Analytical Methods CommiteeCordero-Rando, M.M., Barea-Zamora, M., Barberá-Salvador, J.M., Naranjo-Rodríguez, I., Munoz-Leyva, J.A., Cisneros, J.L.H.-H., (1999) Mikrochim. Acta, 132, p. 7Yang, C., (2004) Microchim. Acta, 148, p. 8

Reactive Oxygen And Nitrogen Species, Antioxidants And Markers Of Oxidative Damage In Human Blood: Main Analytical Methods For Their Determination [espécies Reativas De Oxigênio E De Nitrogênio, Antioxidantes E Marcadores De Dano Oxidativo Em Sangue Humano: Principais Métodos Analíticos Para Sua Determinação]

We review here the chemistry of reactive oxygen and nitrogen species, their biological sources and targets; particularly, biomolecules implicated in the redox balance of the human blood, and appraise the analytical methods available for their detection and quantification. Those biomolecules are represented by the enzymatic antioxidant defense machinery, whereas coadjutant reducing protection is provided by several low molecular weight molecules. Biomolecules can be injured by RONS yielding a large repertoire of oxidized products, some of which can be taken as biomarkers of oxidative damage. Their reliable determination is of utmost interest for their potentiality in diagnosis, prevention and treatment of maladies.30513231338Schafer, F.Q., Buettner, G.R., (2001) Free Radical Biol. Med, 30, p. 1191Grow, A.J., Ischiropoulos, H.J., (2001) J. Cell. Physiol, 187, p. 277Finkel, T., Holbrook, N.J., (2000) Nature (London, U. K.), 408, p. 239Wiseman, H., (1996) J. Nutr. 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Electrochemical Study Of Methyl 2-[p-nitrophenyi(hydroxy)methyl]acrylate, An Anticancer Drug, In The Presence Of Gsh And Dsdna

Electrochemical experiments (CV, DPV, SWV, CPE) with methyl 2-[p-nitrophenyl(hydroxy) methyl] acrylate (1) were performed in protic (EtOH + phosphate buffer 1:9, 0.1 mol L-1, pH 6.9 and EtOH + phosphate buffer: 1:9, 0.1 mol L1, pH 9.4) and aprotic (DMF + TBAP, 0.1 mol L-1) media. The reduction behaviours were typical of nitroaromatics, with an additional wave, in aprotic medium, related to the reduction of the olefin. Electrolysis, in protic media, furnished a reduced dimer. The incubation of 1 into a dsDNA biosensor revealed, that, after reduction of the nitroaromatic function, diagnostic oxidation peaks of the nucleobases were observed, indicative of interaction between them. GSH influenced the reduction behaviour of 1. Direct reduction of 1, in phosphate buffer, pH 9.38, to a stable nitroso/GSH adduct is facilitated. These electrochemical results help in the understanding of the anticancer activity of 1 that can be considered a hypoxia targeted bioreductive agent with a glutathione depleting function. copyright The Electrochemical Society.329137146Rauf, S., Gooding, J.J., Akhtar, K., Ghauri, M.A., Rahman, M., Anwar, M.A., Khalid, A.M., (2005) J. Pharm. Biomed. Anal, 37, p. 205Russo, A., Degraff, W., Friedman, N., Mitchell, J.B., (1986) Cancer Res, 46, p. 2845Tew, K.D., (1994) Cancer Res, 54, p. 4313Berube, L.R., Farah, S., McClelland, R.A., Rauth, A.M., (1992) Int. J. Radiat. Oncol. Biol. Phys, 22, p. 817Griffith, O.W., Meister, A., (1979) J. Biol. Chem, 254, p. 7558Williamson, J.M., Boettcher, B., Meister, A., (1982) Proc. Natl. Acad. Sci. USA, 79, p. 6246McCarthy, T.J., Hayes, E.P., Schwartz, C.S., Witz, G., (1994) Fundam. Appl. Toxicol, 22, p. 543Kohn, L.K., Pavam, C.H., Veronese, D., Coelho, F., De Carvalho, J.E., Almeida, W.P., (2006) Eur. J. Med. Chem, 41, p. 738De Abreu, F.C., Ferraz, P.A.L., Goulart, M.O.F., (2002) J. Braz. Chem. Soc, 13, p. 19Squella, J.A., Bollo, S., Núñez-Vergara, L.J., (2005) Current Org. Chem, 9, p. 565Julião, M.D.D.S., Ferreira, E.I., Ferreira, N.G., Serrano, S.H.P., (2006) Electrochim. Acta, 51, p. 5080A. M. O. Brett, M.O.F.Goulart and F.C. de Abreu, Biosens. Bioelectron., 17, 913 (2002)Brett, A.M.O., Serrano, S.H.P.J., Piedade, A.P., (1999) Comprehensive Chemical Kinetics, 37, pp. 91-119. , R. G. Compton and H. G. Hancock, Editors, Elsevier: AmsterdamCoelho, F., Almeida, W.P., Mateus, C.R., Veronese, D., Lopes, E.C.S., Silvira, G.P.S., Rossi, R.C., Pavam, C.H., (2002) Tetrahedron, 58, p. 7437Lund, H., Cathodic Reduction of Nitro and Related Compounds (2001) Organic Electrochemistry, p. 389. , 4th Ed, H. Lund and O. Hammerich, Editors, p, Marcel Dekker, New YorkMcClelland, R.A., (1990) Selective Activation of Drugs by Redox Processes, p. 125. , G.E. Adams, A. Breccia, E.M. Fielden and P. Wardman, Editors, p, Plenum Press, New YorkTocher, J.H., Edwards, D.I., (1995) Biochem. Pharmacol, 50, p. 136

Electrochemical Study Of Methyl 2- [p -nitrophenyl(hydroxy)methyl]acrylate

Electrochemical experiments with methyl 2- [p -nitrophenyl(hydroxy)methyl] acrylate (1) were performed in protic (EtOH+phosphate buffer 1:9, 0.1 mol L-1, pH 6.9; EtOH+phosphate buffer+NaOH 1:9, 0.1 mol L-1 or 0.2 mol L-1, pH 9.4 and EtOH+ NaHCO3 +NaOH 2:8, 0.18 mol L-1, pH 9.6) and aprotic [dimethylformamide (DMF)+tetrabutylammonium perchlorate (TBAP), 0.1 mol L-1] media. The primary reduction behavior in aprotic medium was typical of nitroaromatics along with an additional wave related to the reduction of the acrylate function. Kinetic analysis carried out in aprotic and aqueous basic media pointed out to the high stability of the electrogenerated nitro radical anion, especially in DMF+TBAP. Reduced (GSH) and oxidized (GSSG) gluthatione in phosphate buffer influenced the reduction behavior of 1, due mainly to protonation effects. Direct reduction of 1, in the presence of GSH, led to a transient nitroso-GS adduct. In the presence of GSSG, hydrogen-bonding-associated GSSG-hydroxylamine was the main product. Electrochemical studies of 1, in the presence of oxygen, showed no chemical reactivity between O2 and 1 -. These electrochemical results help in the understanding of the anticancer activity of 1 that can be considered a bioreductive agent with a glutathione depleting function. © 2007 The Electrochemical Society.15411P121P129Garret, M.D., Workman, P., (1999) Eur. J. Cancer, 35, p. 2010Russo, A., Degraff, W., Friedman, N., Mitchell, J.B., (1986) Cancer Res., 46, p. 2845Tew, K.D., (1994) Cancer Res., 54, p. 4313Griffith, O.W., Meister, A., (1979) J. Biol. Chem., 254, p. 7558Williamson, J.M., Boettcher, B., Meister, A., (1982) Proc. Natl. Acad. Sci. U.S.A., 79, p. 6246Kirlin, W.G., Cai, J., Thompson, S.A., Diaz, D., Kavanagh, T.J., Jones, D.P., (1999) Free Radic Biol. Med., 27, p. 1208Powis, G., Gasdaka, J.R., Baker, A., (1997) Adv. Pharmacol. (San Diego), 38, p. 329Berube, L.R., Farah, S., McClelland, R.A., Rauth, A.M., (1992) Int. J. Radiat. Oncol., Biol., Phys., 22, p. 817McCarthy, T.J., Hayes, E.P., Schwartz, C.S., Witz, G., (1994) Fundam. Appl. Toxicol., 22, p. 543Kohn, L.K., Pavam, C.H., Veronese, D., Coelho, F., De Carvalho, J.E., Almeida, W.P., (2006) Eur. J. Med. Chem., 41, p. 738Kundu, M.K., Sundar, N., Kumar, S.K., Bhat, S.V., Biswas, S., Valecha, N., (1999) Bioorg. Med. Chem. Lett., 9, p. 731De Abreu, F.C., Ferraz, P.A.L., Goulart, M.O.F., (2002) J. Braz. Chem. Soc., 13, p. 19Squella, J.A., Bollo, S., Núez-Vergara, L.J., (2005) Curr. Org. Chem., 9, p. 565. , 1385-2728 10.2174/1385272053544380Da Julião, D.M.S., Ferreira, E.I., Ferreira, N.G., Serrano, S.H.P., (2006) Electrochim. Acta, 51, p. 5080Tocher, J.H., Edwards, D.I., (1995) Biochem. Pharmacol., 50, p. 1367Bollo, S., Gunckel, S., Nunez-Vergara, L.J., Chauviere, G., Squella, J.A., (2005) Electroanalysis, 17, p. 134Coelho, F., Almeida, W.P., Mateus, C.R., Veronese, D., Lopes, E.C.S., Silveira, G.P.S., Rossi, R.C., Pavam, C.H., (2002) Tetrahedron, 58, p. 7437Krezel, A., Bal, W., (2003) Org. Biomol. Chem., 1, p. 3885Olmstead, M.L., Nicholson, R.S., (1969) Anal. Chem., 41, p. 862Bard, A.J., Faulkner, R.L., (2000) Electrochemical Methods, Fundamentals and Applications, p. 240. , 2nd ed., Wiley and Sons, New YorkCarbajo, L., Bollo, S., Núez-Vergara, L.J., Campero, A., Squella, J.A., (2002) J. Electroanal. Chem., 531, p. 187Lund, H., (2001) Organic Electrochemistry, p. 389. , 4th ed., H.Lund and O.Hammerich, Editors, Marcel Dekker, New YorkGrimshaw, J., (2001) Organic Electrochemistry: An Introduction and A Guide., pp. 411-434. , 3rd ed., H.Lund, and O.Hammerich, Editors, Marcel Dekker, New YorkZuman, P., Fijalek, Z., Dumanovic, D., Suznjevic, D., (1992) Electroanalysis, 4, p. 783Nicholson, R.S., Shain, I., (1964) Anal. Chem., 36, p. 706McClelland, R.A., (1990) Selective Activation of Drugs by Redox Processes, p. 125. , G. E.Adams, A. Breccia, E. M.Fielden, and P.Wardman, Editors, Plenum Press, New YorkWardman, P., (1986) Environ. Health Perspect., 64, p. 309Aguilar-Martinez, M., MacÍas-Ruvalcaba, N.A., Bautista-Martínez, J.A., Gómez, M., González, F.J., González, I., (2004) Curr. Org. Chem., 8, p. 1721Miller, C., Folkes, L.K., Mottley, C., Wardman, P., Mason, R.P., (2002) Arch. Biochem. Biophys., 397, p. 113Eyer, P., (1979) Chem. Biol. Interact., 24, p. 227Kazanis, S., McClelland, R., (1992) J. Am. Chem. Soc., 114, p. 3052Clancy, R., Cederbaum, A.I., Stoyanovsky, D.A., (2001) J. Med. Chem., 44, p. 2035Singh, R.J., Hogg, N., Joseph, I., Kalyanaraman, B., (1996) J. Biol. Chem., 271, p. 18596Soul̀re, L., Sturm, J.-C., Núez-Vergara, L.J., Hoffmann, P., Ṕrí, J., (2001) Tetrahedron, 57, p. 7137How, N., (2000) Free Radic Biol. Med., 28, p. 147

Growth Inhibitory Effects Of 3'-nitro-3-phenylamino Nor-beta-lapachone Against Hl-60: A Redox-dependent Mechanism

In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO 2) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF 4) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO 2. QPhNO 2 caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO 2 treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. 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