Abstract
The potential value of selective and non-selective COX-2 inhibitors in preventing some of the biochemical changes induced by ionizing radiation was studied in rats exposed to carrageenan-induced paw edema and 6-day-old air pouch models. The animals were exposed to different exposure levels of γ-radiation, namely either to single doses of 2 and 7.5 Gy or a fractionated dose level of 7.5 Gy delivered as 0.5 Gy twice weekly for 7.5 weeks. The inflammatory response produced by carrageenan in irradiated rats was markedly higher than that induced in non-irradiated animals, and depended on the extent of irradiation. Celecoxib, a selective COX-2 inhibitor, in doses of 3, 5, 10, and 15 mg/kg was effective in reducing paw edema in irradiated and non-irradiated rats in a dose-dependent manner as well as diclofenac (3 mg/kg), a non-selective COX inhibitor. Irradiation of animals before the induction of the air pouch by an acute dose of 2 Gy led to a significant increase in leukocytic count, as well as in the level of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), LTB4, PGE2 (as an index of COX-2 activity), TXB2 (as an index of COX-1 activity), and the plasma level of MDA. This increase in level of these parameters was more marked than that observed in the non-irradiated animals subjected to the inflammagen. The blood GSH level was not affected by the dose of irradiation used, whereas superoxide dismutase (SOD) activity was suppressed. In many respects, celecoxib (5 mg/kg) was as potent as diclofenac in decreasing the elevated levels of IL-6, IL-1β, TNF-α, LTB4, PGE2, but lacked any significant effect on TXB2 level. Since it is mostly selective for COX-2 with a rare effect on COX-1 enzyme, both drugs at the selected dose levels showed no effect on level of MDA, GSH, and SOD activity.
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References
Aarden L, Helle M, Boeje L, Pascual-Salcedo D, De Groot E (1991) Differential induction of IL-6 production in monocytes, endothelial cells and smooth muscle cells. Eur Cytokine Netw 2:12–115
Appleton I, Tomlinson A, Colville-Nash PR, Willoughby DA (1993) Temporal and spatial immunolocalization of cytokines in murine chronic granulomatous tissue. Implications for their role in tissue development and repair processes. Lab Invest 69:369–372
Barcellos-Hoff MH (1998) How do tissues respond to damage at cellular level? The role of cytokines in irradiated tissues. Radiat Res 150:109–120
Berroud A, Le Roy A, Voisin P (1996) Membrane oxidative damage induced by ionizing radiation detected by fluorescence polarization. Radiat Environ Biophys 35:289–295
Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Chevion S, Or R, Berry EM (1999) The antioxidant status of patients subjected to total body irradiation. Biochem Mol Biol Int 47:1019–1027
Choy H, Milas L (2003) Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance? J Natl Cancer Inst 95:1440–1452
Cole AT, Hawkey CJ, Salter K, Sokal M (1993) In vivo rectal inflammatory mediator changes with radiotherapy to the pelvis. Gut 34:1210–1214
Dannenberg AJ, Altorki NK, Boyle JO, Dany C, Howe LR, Weksler BB, Subbaramaiah K (2001) Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2:544–551
de Groot DJA, de Vries EGE, Groen HJM, de Jong S (2007) Non-steroidal anti-inflammatory drugs to potentiate chemotherapy effects: from lab to clinic. Oncol Hematol 61:52–69
Di Rosa M, Willoughby DA (1971) Screens for anti-inflammatory drugs. J Pharm Pharmacol 23:297–298
Di Rosa M, Papadimitrou JM, Willoughby DA (1971) A histopathological and pharmacological analysis of the mode of action of non-steroidal anti-inflammatory drugs. J Path 105:239–256
Dinarello CA (1997) Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 11:91–103
Dokmeci D, Akpolat M, Aydogdu N, Uzal C, Doganay L, Turan FN (2006) The protective effect of L-carnitine on ionizing radiation-induced free oxygen radicals. Scand J Lab Anim Sci 33:75–83
Eisen V, Walker DI (1976) Effect of ionizing radiation on prostaglandin-like activity in tissues. Br J Pharmacol 57:527–532
El-Ghazaly MA (1996) The effect of aqueous propolis extract on cellular migration, prostaglandins and histamine release in irradiated rats. J Egypt Soc Toxicol 16:69–73
El-Ghazaly MA, Khayyal MT (1995) The use of aqueous propolis extract against radiation-induced damage. Drugs Exp Clin Res 21:229–236
El-Ghazaly MA, Ramadan LA (1996) Alteration in some metabolic functions in albino rats after irradiation and possible role of thiola. J Egypt Soc Toxicol 16:105–109
El-Ghazaly M, Kenawy S, Khayyal MT, Roushdy H, Saleh S (1985) Effect of exposure to radiation on the inflammatory process and its influence by diclofenac. Br J Pharmac 85:45–50
El-Ghazaly M, Saleh S, Kenawy S, Roushdy HM, Khayyal MT (1986) The protective value of piroxicam on the enhanced inflammatory response after whole body irradiation. Pharmacol Res Commun 18:563–580
Ewing D, Jones SR (1987) Superoxide removal and radiation protection in bacteria. Arch Biochem Biophys 254:53–62
FitzGerald TJ, Aronowitz J, Giulia CM, Fisher G, Kadish S, Lo YC, Mayo C, McCauley S, Meyer J, Pieters R, Sherman A (2006) The effect of radiation therapy on normal tissue function. Hematol Oncol Clin North Am 20(1):141–163
Hahn GL, Menconi MJ, Cahill M, Polgar P (1983) The influence of gamma radiation on arachidonic acid release and prostacyclin synthesis. Prostaglandins 25:783–791
Hallahan DE, Spriggs DR, Beckett MA, Kufe DW, Weichselbaum RR (1989) Increased tumor necrosis factor a mRNA after cellular exposure to ionizing radiation. Proc Natl Acad Sci USA 86:10104–10107
Halliwell B (1999) Oxygen and nitrogen are pro-carcinogens damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 443:37–52
Han Y, Son SJ, Akhalaia M, Platonov A, Son HJ, Lee KH, Yun YS, Song JY (2005) Modulation of radiation-induced disturbances of antioxidant defense systems by ginsan. Evid Based Complement Altern Med 2:529–536
Kemper F, Ameln G (1959) Eine neue elektrische Methode Zur Messung von Volumina, Drucken und anderem sowie ein Beispiel ihrer Anwendung. Z Gesamte Exp Med 131:407–411
Khayyal MT, El-Ghazaly MA, Abdallah DM, Okpanyi N, Kelber O, Weiser D (2005) Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract. Arzneimittelforschung 55:677–687
Ku EC, Lee W, Kothari HV, Scholer DW (1986) Effect of diclofenac sodium on the arachidonic acid cascade. Am J Med 80:18–23
Lee TK, Stupans I (2002) Radioprotection: the non-steroidal anti-inflammatory drugs (NSAIDs) and prostaglandins. J Pharm Pharmacol 54:1435–1445
Malik A, Lo S (1996) Vascular endothelial adhesion molecules and tissue inflammation. Pharmacol Rev 48:213–229
Manoharan S, Kolanjiappan K, Suresh K, Panjamurthy K (2005) Lipid peroxidation and antioxidants status in patients with oral squamous cell carcinoma. Indian J Med Res 122:529–534
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Masferrer JL, Zweifel BS, Manning PT, Hauser SD, Leahy KM, Smith WG, Isakson PC, Seibert K (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci USA 9:3228–3232
McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055
Michalowski AS (1994) On radiation damage to normal tissues and its treatment II. Anti-inflammatory drugs. Acta Oncol 33:139–157
Milas L, Hanson WR (1995) Eicosanoids and radiation. Eur J Cancer 31:1580–1585
Minhas HS, Thornalley PJ (1995) Comparison of the delivery of reduced glutathione into P388D1 cells by reduced glutathione and its mono- and diethyl ester derivatives. Biochem Pharmacol 49:1475–1482
Nathan C (2002) Points of control in inflammation. Nature 420:846–885
Ohara M, Sawa T (1988) Current topics in the regulation of prostanoids-2. The interaction with cytokines and nitric oxide. Masui 47:1471–1477
Panosyan AG, Grigoryan GK, Arakelyan ON, Mkhitaryan GS (1992) Animal blood prostaglandins following acute radiation exposure. Med Radiol 37:48–51
Plevova P (2002) Modulation of radiotherapy- and chemotherapy-induced normal tissue response as prophylaxis of their side effects. Radiol Oncol 36:33–40
Roos D, Law SK (2001) Hematologically important mutations: leukocyte adhesion deficiency. Blood Cells Mol Dis 27:1000–1004
Sabichi AL, Lippman SM (2004) COX-2 inhibitors and other non steroidal anti-inflammatory drugs in genitourinary cancer. Semin Oncol 31:36–44
Samad TA, Sapirstein A, Woolf CJ (2002) Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets. Trends Mol Med 8:390–396
Sarkar SR, Singh LR, Uniyal BP, Chaudhuri BN (1983) Effect of whole body gamma radiation on reduced glutathione contents of rat tissues. Strahlentherapie 159:32–33
Sedgwick AD, Lees P (1986) Studies of eicosanoid production in the air pouch model of synovial inflammation. Agents Actions 18:429–438
Sedgwick AD, Sin YM, Edwards JCW, Willoughby DA (1983) Increased inflammatory reactivity in newly formed lining tissue. J Pathol 141:483–495
Sedgwick AD, Sin YM, Mackay AR, Al-Duaij A, Willoughby DA (1984) Studies of the mode of action of non-steroidal anti-inflammatory drugs using a model of facsimile synovium. J Pharm Pharmacol 36:171–174
Sherman ML, Datta R, Hallahan DE, Weichselbaum RR, Kufe DW (1991) Regulation of tumor necrosis factor gene expression by ionizing radiation in human myeloid leukemia cells and peripheral blood monocytes. J Clin Invest 87:1794–1797
Steinauer KK, Gibbs I, Ning S, French JN, Armstrong J, Knox SJ (2000) Radiation induces upregulation of cyclooxygenase-2 (COX-2) protein in PC-3 cells. Int J Radiat Oncol Biol Phys 48:325–328
Sun J, Chen Y, Li M, Ge Z (1998) Role of antioxidant enzymes on ionizing radiation resistance. Free Radic Biol Med 24:586–593
Trocha PJ, Catravas GN (1980) Prostaglandin levels and lysosomal enzyme activities in irradiated rats. Int J Radiat Biol Relat Stud Phys Chem Med 38:503–511
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84
Van der Meeren A, Monti P, Lebaron-Jacobs L, Marquette C, Gourmelon P (2001) Characterization of the acute inflammatory response after irradiation in mice and its regulation by interleukin-4. Radiat Res 155:858–865
Vinegar R, Schreiber W, Hugo R (1969) Biphasic development of carrageenan edema in rats. J Pharmacol 166:96–103
Weisiger RA, Fridovich I (1973) Mitochondrial superoxide dismutase: site of synthesis and intramitochondrial location. J Biol Chem 248:4793–4796
Willis AL (1969) Measurement of inflammatory mediators by cascade superfusion of inflammatory exudates. J Pharm Pharmacol 21:126–128
Winter CA, Risley EA, Nuss GW (1962) Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 111:544–547
Woloschak GE, Chang-Liu CM, Jones PS, Jones CA (1990) Modulation of gene expression in Syrian hamster embryo cells following ionizing radiation. Cancer Res 50:339–344
Yoshioka T, Kawada K, Shimada T, Mori M (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol 135:372–376
Yukawa O, Nagatsuka S, Nakazawa T (1983) Reconstitution studies on the involvement of radiation-induced lipid peroxidation in damage to membrane enzymes. Int J Radiat Biol Relat Stud Phys Chem Med 43:391–398
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Khayyal, M.T., El-Ghazaly, M.A., El-Hazek, R.M. et al. The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats. Inflammopharmacol 17, 255–266 (2009). https://doi.org/10.1007/s10787-009-0014-z
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DOI: https://doi.org/10.1007/s10787-009-0014-z