Abstract
Electron spin resonance (ESR) was used to investigate the reaction of aspirin toward reactive oxygen species, such as hydroxyl radicals (·OH), superoxide radicals ( -O2 ) and H2O2. The Fenton reaction (Fe(II) + H2O2 ---> FE(III) + -OH + OR) was used as a source of -OH radicals. The results show that aspirin is an efficient -OH radical scavenger with a reaction rate constant of k = 3.6 x 1010 M-1sec-1, which is faster than several well established antioxidants, such as ascorbate, glutathione and cysteine. However, aspirin is not a good scavenger for -O2 or H2O2. Through its antioxidant property, aspirin exhibited a protective effect against silica-induced lipid peroxidation and DNA strand breakage. Aspirin also inhibited the activation of nuclear transcription factor-κb induced by silica, lipopolysaccharide or the transition metal, Fe(II), as demonstrated by electrophoretic mobility shift assay. The results show that aspirin functions as an antioxidant via its ability to scavenge -OH radicals. This antioxidant property may explain some of its various physiological and pharmacological actions.
Similar content being viewed by others
References
Thun MJ, Namboodiri MM, Heath CW Jr: Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325: 1593–1596, 1991
Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr: Aspirin use and risk of fatal cancer. Can Res 53: 1322–1327, 1993
Kune GA, Kune S, Watson LF: Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Can Res 48: 4399–4404, 1988
Logan RF, Little J, Hawtin PG, Hardcastle JD: Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme. BMJ 307: 285–289, 1993
Narisawa T, Satoh M, Sano M, Takahashi T: Inhibition of initiation and promotion by N-methylnitrosourea-induced colon carcinogenesis in rats by non-steroid anti-inflammatory agent indomethacin. Carcinogenesis 4: 1225–1227, 1983
Metzger U, Meier J, Uhlschmid G, Weihe H: Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer. Dis Colon Rectum 27: 366–369, 1984
Nigro ND, Bull AW, Boyd ME: Inhibition of intestinal carcinogenesis in rats: Effect of difluoromethylomithine with piroxicam or fish oil. J Natl Cancer Inst 77: 1309–1313, 1986
Takahashi M, Furukawa F, Toyoda K, Sato H, Hasegawa R, Imaida K, Hayashi Y: Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with Nnitrosobis( 2-oxopropyl)amine. Carcinogenesis 11: 393–395, 1990
Moorghen M, Ince P, Finney KJ, Sunter JP, Appleton DR, Watson AJ: A protective effect of sulindac against chemically-induced primary colonic tumours in mice. J Path 156: 341–347, 1988
Murasaki G, Zenser TV, Davis BB, Cohen SM: Inhibition by aspirin of N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide-induced bladder carcinogenesis and enhancement of forestomach carcinogenesis. Carcinogenesis 5: 53–55, 1984
Sakata T, Hasegawa R, Johansson SL, Zenser TV, Cohen SM: Inhibition by aspirin of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide initiation and sodium saccharin promotion of urinary bladder carcinogenesis in male F344 rats. Can Res 46: 3903–3906, 1986
Cohen SM, Hasegawa R, Sakata T, Johansson SL: Effect of aspirin on urinary bladder carcinogenesis initiated with N-[4-(5-nitro-2-furyl)3 2-thiazolyl]formamide in rats. Can Res 49: 372–377, 1989
McConnick DL, Madigan MJ, Moon RC: Modulation of rat mammary carcinogenesis by indomethacin. Can Res 45: 1803–1808, 1985
Iuliano L, Colavita AR, Leo R, Pratico D, Violi F: Oxygen free radicals and platelet activation. Free Rad Biol Med 22: 999–1006, 1997
Thome J, Zhang J, Davids E, Foley P, Weijers HG, Wiesbeck GA, Boning J, Riederer P, Gerlach M: Evidence for increased oxidative stress in alcohol-dependent patients provided by quantification of in vivo salicylate hydroxylation products. Alcohol Clin Exp Res 21: 82–85, 1997
Wang Y, Walsh SW: Aspirin inhibits both lipid peroxides and thromboxane in preeclamptic placentas. Free Rad Biol Med 18: 585–591, 1995
Brigham KL: Role of free radicals in lung injury. Chest 89: 859–863, 1986
Barnes PJ: Reactive oxygen species and airway inflammation. Free Rad Biol Med 9: 235–243, 1990
Kehrer JP: Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 23: 21–48, 1993
Jamieson D: Oxygen toxicity and reactive oxygen metabolites in mammals. Free Rad Biol Med 7: 87–108, 1989
Heffner JE, Repine JE: Pulmonary strategies of antioxidant defense. Am Rev Respir Dis 140: 531–554, 1989
McCord JM: Human disease, free radicals, and the oxidant/antioxidant balance. Clin Biochem 26: 351–357, 1993
Kinnula V, Crapo JD, Raivio KO: Generation and disposal of reactive oxygen metabolites in the lung. Lab Invest 73: 3–19, 1995
Halliwell B, Gutteridge JM, Cross CE: Free radicals, antioxidants, and human disease: Where are we now? J Lab Clin Med 119: 598–620, 1992
Sun Y, Oberley LW: Redox regulation of transcriptional activators. Free Rad Biol Med 21: 335–348, 1996
Sen CK, Packer L: Antioxidant and redox regulation of gene transcription. FASEB J 10: 709–720, 1996
Silicosis and silica Disease Committee: Disease associated with exposure to silica and silicosis. Arch Pathol Lab Med 112: 673–720, 1988
International Agency for Research on Cancer: Silica. In: IARC Monographs on the Evaluation of carcinogenic risk of Chemicals to humans, vol 42, Silica and Some Silicates, pp. 39–143, IARC, Lyon, 1987
Shi X, Dalal NS, Hu X, Vallyathan V: The chemical properties of silica particle surface in relation to silica-cell interactions. J Toxicol Environ health 27: 435–454, 1989
Reiser KM, Last JA: Silicosis and fibrogenesis: Fact and artifact. Toxicology 13: 51–72, 1979
Janzen EG, Blackburn BJ: Detection and identification of shoet-lived free radical by an electron spin resonance trapping technique. J Am Chem Soc 90: 5909–5910, 1968
Mottley C, Mason RP: Nitroxide radical adducts in biology: Chemistry, applications, and pitfalls. Biol Magn Reson 8: 489–546, 1989
Shi X, Mao Y, Daniel LN, Safflotti U, Dalal NS, Vallyathan V: Generation of reactive oxygen species by quartz particles and its implication for cellular damage. Appl Occup Environ Hyg 10: 1138–1144, 1995
Shi X, Jiang H, Mao Y, Ye J, Safflotti U: Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine hydroxylation and DNA damage. Toxicology 106: 27–38, 1996
Sun SC, Elwood J, Beraud C, Greene WC: Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA (p65)-mediated induction of the c-rel gene. Mol Cell Biol 14: 7377–7384, 1994
Buettner GR: Spin trapping: ESR parameters of spin adducts. Free Rad Biol Med 3: 259–303, 1987
Buettner, GR: The spin trapping of superoxide and hydroxyl radicals. In: L.W. Oberley (ed). Superoxide Dismutase. Vol. 2. CRC Press, Boca Raton, FL, 1982, pp. 64–81
Morehouse KM, Mason RP: The transition metal-mediated formation of the hydroxyl free radical during the reduction of molecular oxygen by ferredoxin-ferredoxin:NADP+ oxidoreductase. J Biol Chem 263: 1204–1211, 1988
Flinkelstein E, Rosen GM, Rauckman EJ: Spin trapping. Kinetics of the reaction of superoxide and hydroxyl radicals with nitrones. J Am Chem Soc 102: 4994–4999, 1980
Marriott PR, Perkins Mj, Griller D: Spin trapping for hydroxyl radical in water; a kinetics evluation of two popular traps. Can J Chem 58: 803–807, 1980
Vallyathan V, Shi XL, Dalal NS, Irr W, Castranova V: Generation of free radicals from freshly fractured silica dust: Potential role in acute silica-induced lung injury. Am Rev Respir Dis 138: 1213–1219, 1988
Dorfman LM, Adams GE: Reaction rates of hydroxy radical with various substances. National Reference Data service, National Bureau of Standards. No. 46, pp. 1–56
Matsugo S, Yan LJ, Han D, Trischler HJ, Packer L: Elucidation of antioxidant activity of alpha-lipoic acid toward hydroxyl radical. Biochem Biophys Res Commun 208: 161–167,1995
Kopp E, Ghosh S: Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 265: 956–959, 1994
Schreck R, Rieber P, Baeuerle PA: Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J 10: 2247–2258, 1991
Shi X, Dong Z, Huang C, Ma W, Liu K, Ye J, Chen F, Leonard S, Ding M, Castranova V, Vallyathan V: The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-κB. Mol Cell Biochem (In press)
Dong Z, Huang C, Brown RE, Ma WY: Inhibition of activator protein I activity and neoplastic transformation by aspirin. J Biol Chem 272: 9962–9970, 1997
Baeuerle PA: The inducible transcription activator NF-kappa B: Regulation by distinct protein subunits. Bioch Biophys Acta 1072: 63–80, 1991
Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor alpha and interleukin I stimulate the human immunodeficiency virus enhancer by activation of nuclear factor kappa B. Proc Natl Acad Sci USA 86: 2336–2340, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shi, X., Ding, M., Dong, Z. et al. Antioxidant properties of aspirin: Characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-κB activation, and TNF-α production. Mol Cell Biochem 199, 93–102 (1999). https://doi.org/10.1023/A:1006934612368
Issue Date:
DOI: https://doi.org/10.1023/A:1006934612368