Meryem AKPOLAT, Yeter Topçu TARLADAÇALIŞIR, Dikmen DÖKMECİ, Fatma Nesrin TURAN, Mustafa Cem UZAL

Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury

Objective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6): group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy

Keywords:

Whole body irradiation, duodenum, ibuprofen, L-carnitine, hamster,

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Zheng H, Wang J, Koteliansky VE, Gotwals PJ, Hauer-Jensen M. Recombinant soluble transforming growth factor beta type II re- ceptor ameliorates radiation enteropathy in mice. Gastroenterol- ogy 2000;119:1286-96. [CrossRef]
Denham JW, Hauer-Jensen M, Peters LJ. Is it time for a new for- malism to categorise normal tissue radiation injury? Int JRadiat Oncol Biol Phys 2001;50:1105-6. [CrossRef]
Jonathan EC, Bernhard EJ, McKenna WG. How does radiation kill cells? Curr Opin Chem Biol. 1999;3:77-83.
Brennan PC, Carr KE, Seed T, Mccullough JS. Acute and pro- tracted radiation effects on small intestinal morphological pa- rameters. Int J Radiat Biol 1998;73:691-8.
Buell MG, Harding RK. Proinflammatory effects of local abdominal irradiation on rat gastrointestinal tract. Dig Dis Sci 1989;34:390-9. [CrossRef]
Merritt AJ, Potten CS, Watson AJ, Loh DY, Nakayama K, Nakaya- ma K et al. Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Sci 1995;108:2261-71.
Felemovicius I, Bonsack ME, Baptista ML, Delaney JP. Intesti- nal Radioprotection by Vitamin E (Alpha-Tocopherol). Ann Surg 1995;222:504-10. [CrossRef]
Kennedy TP, Rao NV, Noah W, Michael JR, Jafri MH Jr, Gurtner GH et al. Ibuprofen prevents oxidant lung injury and in vitro lipid peroxidation by chelating iron. J Clin Invest 1990;86:1565-73. [CrossRef]
Zapolska-Downar D, Zapolska-Downar A, Bukowska H, Galka H, Naruszewicz M. Ibuprofen protects low density lipoproteins against oxidative modification. Life Sci 1999;65:2289-303. [CrossRef]
Hamburger SA, McCay PB. Spin trapping of ibuprofen radicals: evidence that ibuprofen is a hydroxyl radical scavenger. Free Radic Res Commun 1990;9:337-42. [CrossRef]
Schmeling DJ, Drongowski RA, Coran AG. The beneficial effects of ibuprofen on a lethal live E. coli septic shock model and the re- lationship of these effects to superoxide radical production. Prog Clin Biol Res 1989;299:53-61.
Dokmeci D, Akpolat M, Aydogdu N, Uzal C, Turan NF. The modi- fying effect of ibuprofen on total body irradiation-induced el- evation of oxidative reactions in male hamsters. Acta Med Biol 2004;52:67-72.
Izgut-Uysal VN, Agac A, Derin N. Effect of L-carnitine on car- rageenan-induced inflammation in aged rats. Gerontology 2003;49:287-92.
Onem G, Aral E, Enli Y, Oguz EO, Coskun E, Aybek H et al. Neu- roprotective effects of L-carnitine and vitamin E alone or in com- bination against ischemia-reperfusion injury in rats. J Surg Res 2006;131:124-30. [CrossRef]
Dokmeci D, Akpolat M, Aydogdu N, Doganay L, Turan FN. L- carnitine inhibits ethanol-induced gastric mucosal injury in rats. Pharmacol Rep 2005;57:481-8.
Dokmeci D, Akpolat M, Aydogdu N, Uzal C, Doganay L, Turan FN. The Protective Effect of L-carnitine on Ionizing Radiationinduced Free Oxygen Radicals.Scand J Lab Anim Sci 2006;33:75-83.
Palayoor ST, Bump EA, Calderwood SK, Bartol S, Coleman CN. Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin Cancer Res 1998;4:763-71.
Arockia Rani PJ, Panneerselvam C. Carnitine as a free radical scavenger in aging. Exp Gerontol. 2001;36:1713-26.
Pisano C, Pratesi G, Laccabue D, Zunino F, Lo Giudice P, Bellucci A et al. Paclitaxel and Cisplatin-induced neurotoxicity: a protec- tive role of acetyl-L-carnitine. Clin Cancer Res 2003;9:5756-67.
Feurgard C, Boehler N, Férézou J, Sérougne C, Aigueperse J, Gourmelon P et al. Ionizing radiation alters hepatic cholesterol metabolism and plasma lipoproteins in Syrian hamster. Int J Ra- diat Biol 1999;75:757-66.
Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mu- cosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970;101:478-83.
Driák D, Osterreicher J, Vávrová J, Reháková Z, Vilasová Z. Morphological changes of rat jejunum after whole body gam- ma-irradiation and their impact in biodosimetry. Physiol Res 2008;57:475-9.
Osborne JW, Prasad KN, Zimmerman GR. Changes in the rat intestine after X-irradiation of exteriorized short segments of il- eum. Radiat Res 1970;43:131-42. [CrossRef]
Hagemann RF, Lesher S. Intestinal crypt survival and total and per re- sponse and animal lethality. Radiat Res 1971;47:159-67. [CrossRef]
Kanter M, Akpolat M. Vitamin C protects against ionizing radia- tion damage to goblet cells of the ileum in rats. Acta Histochem 2008;110:481-90. [CrossRef]
Potten CS, Booth C, Pritchard DM. The intestinal epithelial stem cell: The mucosal governor. Int J Exp Pathol 1997;78:219-43. [CrossRef]
Potten CS, Owen G, Roberts SA. The temporal and spatial changes in cell proliferation within the irradiated crypts of the murine small intestine. Int J Radiat Biol 1990;57:185-99.
Carr KE, McCullough JS, Nelson AC, Hume SP, Nunn S, Kamel HM. Relationship between villous shape and mural structure in neutron irradiated small intestine. Scanning Microsc 1992;6:561-72.
Smith DH, De Cosse JJ. Radiation damage to the small intestine. World J Surg 1986;10:189-94. [CrossRef]
Teicher BA, Bump EA, Palayoor ST, Northey D, Coleman CN. Signal transduction inhibitors as modifiers of radiation therapy in human prostate carcinoma xenografts. Radiat Oncol Invest 1996;4:221-30. [CrossRef]
Mansour HH. Protective role of carnitine ester against radiation- induced oxidative stres in rats. Pharmacol Res 2006;54:165-71. [CrossRef]
Fajardo LF. Pathology of Radiation Injury. New York: Masson Pub- lishing; 1982.
Österreicher J, Driak D, Pruchova S, Vilasova Z. Radiation en- teritis: time- and dose-dependent reduction of jejunal crypts in the model of irradiated rats (in Czech). Military Medical Sheets 2005;74:77-80.