DENEYSEL ALKALİ ÖZOFAGUS YANIKLARINDA ALLOPÜRİNOL KULLANIMININ ETKİNLİĞİ

Başlık: DENEYSEL ALKALİ ÖZOFAGUS YANIKLARINDA ALLOPÜRİNOL KULLANIMININ ETKİNLİĞİ
Yazar: ozer makay
Yazar-email: ozer.makay@ege.edu.tr
Kurum: EGE ÜNIVERSITESI TIP FAKÜLTESI, GENEL CERRAHI AD
Yil: 2005
Anahtar: kostik özofagus yanığı, serbest oksijen radikalleri, nitrik oksit, ksantin oksidaz, allopürinol
Ozet: Amaç : Kostik özofagus yanıklarının tedavisinde, darlık gelişmesini engellemeye yönelik bir çok tedavi yöntemi bildirilmiştir. Ancak, bütün bu tedavilere rağmen ciddi yanıklardan sonra gelişen darlık hala kaçınılmaz bir sorundur. Diğer taraftan, kostik yanığı takiben, akut nekrotik faz olarak bilinen dönemde, serbest oksijen radikallerinin özofagus dokusunda arttığı, ksantin oksidaz enziminin bunda rolü olduğu bilinmektedir. Bu amaçla, bu enzimi inhibe eden allopürinol’ün oksidatif stres ve striktür gelişimi üzerindeki etkilerini araştırmayı amaçladık.
Gereç ve yöntem: Çalışmada 60 adet Wistar albino sıçan, her birinde 10 adet olmak üzere 6 gruba ayrılarak çalışıldı. Grup A, B ve C’de kostik yanığın akut dönemdeki etkileri, Grup X, Y ve Z’de ise geç dönemde darlık oluşumu üzerindeki etkileri araştırıldı. Grup A ve X’ teki hayvanlara sham operasyonu uygulanırken, diğer grupları oluşturan hayvanlarda, Gehanno tarafından tarif edilen yöntemin modifikasyonu ile 1ml %37.5’luk NaOH solüsyonu ile standart kostik özofagus yanığı oluşturuldu. Grup B ve Y’deki hayvanlara herhangi bir tedavi uygulanmazken, Grup C ve Z’dekilere allopürinol (40mg/kg; intraperitoneal) tedavisi uygulandı. Akut dönemdeki etkiler, doku malondialdehit (MDA), nitrik oksit (NO) ve glutatyon (GSH) düzeyleri, geç dönemdeki etkiler hidroksiprolin seviyeleri ve histopatolojik hasar skoru ve stenoz indeksi ile değerlendirildi.
Bulgular: Doku GSH düzeyi, A grubu ile karşılaştırıldığında, B grubunda daha yüksek saptanırken (1.37 ± 0.92’ye 1,90 ± 0.95 mg/g yaş doku), C grubunda daha düşük saptandı (1.37 ± 0.92’ye 1,35 ± 0.65 mg/g yaş doku), (p>0.05). Doku NO düzey ortalaması, A grubu ile karşılaştırıldığında B grubunda azaldı (2.99 ± 2.09’a 1,26 ± 0.78 µmol/g yaş doku), (p>0.05). NO düzeyi, C grubunda A grubunun ortalaması altına düşmekle birlikte gruplar arasında anlamlı fark saptanmadı (p>0.05). Doku MDA düzeyi, A grubuna göre B grubunda artış gösterdi (407.5 ± 183.6’ya 960.4 ± 384.8 nmol/g yaş doku) (p<0.05). Tedavi grubunda ise doku MDA düzeyleri azaldı (546.1 ± 338.2 nmol/g yaş doku), (p>0.05). Hidroksiprolin düzeyleri ve stenoz indeksi açısından gruplar arasında anlamlı fark saptanmadı (p>0.05). Grup Y’nin histopatolojik hasar skoru, X ve Z gruplarının değerleri ile karşılaştırıldığında bu gruptaki yüksek skorun anlamlı olduğu belirlendi (p<0.05).
Sonuç: Kostik özofagus hasarında allopürinol’ün etkisinin literatürde ilk kez araştırıldığı bu çalışmada ilaç, erken dönemde GSH, NO ve MDA düzeylerini çeşitli derecelerde etkilemiş ve MDA’nın doku düzeylerini azaltmıştır. Allopürinol, bu modelde kronik dönemde gelişen özofageal fibrozisi anlamlı şekilde azaltmaktadır.
Kaynak: 1. Karaoğlu A, Özütemiz Ö, İlter T. Caustic ingestion injuries: evaluation of 108 cases. Turk J Gastroenterol. 1998;1:55-60.
2. Wasserman RL, Ginsburg CM. Caustic substance injuries. J Pediatr. 1985;107:196-74.
3. Millar AJW, Cywes S. Caustic strictures of esophagus. O’Neill JA Jr., Rowe MI, Pediatric Surgery. Beşinci baskı, St Louis, Mosby, 1998:969-79.
4. Kikendall JN. Caustic ingestion injuries. Gastroenterol Clin North Am. 1991;20:847-57.
5. Peter M, Loeb PM, Eisenstein AM. Caustic injury to the upper gastrointestinal tract. Sleisenger, Fordtran, Gastrointestinal disease. Altıncı baskı, W. B. Saunders, 1998:335-42.
6. www.emedicine.com/emerg/topic86.htm (eMedicine – Eric Kardon. Toxicity, Caustic Ingestions)
7. Douglas O, Fanigel M, Fennerty B. Miscellaneous disease of the esophagus. Yamada, Textbook of Gastroenterology. Üçüncü baskı, Lippincott William & Wilkins 1999:1316-8.
8. Peters JH, DeMeester TR. Esophagus and diaphragmatic hernia. Schwartz, Principles of surgery. Altıncı baskı, McGraw-Hill. 1994:1043-122.
9. http://www.sums.ac.ir/semj/vol4/jan2003/causticinj.htm (Alinejad A. Caustic injury to the upper gastrointestinal tract)
10. Makela JT, Laitinen S, Salo JA. Corrosion injury of the upper gastrointestinal tract after swallowing strong alkali. Eur J Surg. 1998;164:575-80.
11. Gorman RL, Khin Maung Gyi MT, Klein Schwartz W, et al. Initial symptoms as predictors of esophageal injury in alkaline corrosive ingestion. Am J Emerg Med. 1992;10:189-94.
12. Mutaf O. Özofagus yanıkları. Çağdaş Pratisyen 1979;3:6.
13. http://www.utmb.edu/oto/medicalstudent.dir/deskin/pedi-indigest.htm (Deskin RW. Caustic ingestions, junior surgery lecture)
14. Ramasamy K, Gumaste VV. Corrosive ingestion in adults. J Clin Gastroenterol. 2003;37:119-24.
15. Cotran RS, Kumar V, Collins T. Robbins, Pathologic bases of disease. Altıncı baskı, Philadelphia. W.B. Saunders, 1999:103-11.
16. Price SA, Wilson LMC. Patho-physiology. New York, McGraw-Hill, 1978:38-45
17. Guyton AC. Human physiology and mechanisms of disease. Dördüncü baskı, Philadelphia. W.B. Saunders, 1987:486-91.
18. Yağmurlu A, Dindar H, Gürsel M, Hasırcı V. Macrophage suicide approach: new expectation for the prevention of stricture formation in the esophagus. Onaltıncı ulusal çocuk cerrahisi kongresi, 1998, S63. (http//:kudu.sim.net.tr/cem/OT9.html)
19. Kazancı F, Amanvermez R, Bernay F, Yıldız L, Arıtürk E, Gürses N. Koroziv özofagus yanığında oluşan akut enflamasyonda nitrik oksit, lipit peroksidasyon ve antioksidan ilişkisi. (http//:kudu.sim.net.tr/cem/OT9.html)
20. Bayol Ü. Gastroözofageal reflü hastalığı ve özofagus striktürlerinin tedavisi – Pediatrik toraks derneği ilkbahar toplantısı, Workshop Nisan 2003, İzmir.
21. Cohen IK, Diegelman RF, Crossland MC. Wound care and wound healing. Schwartz, Principles of surgery. Altıncı baskı, McGraw Hill. 1994:278-303.
22. Zakim, Boyer. Hepatology, Volüm 1. Dördüncü baskı, Saunders, Philadelphia 2003:347-394
23. Zabel DD, Kunt TK, Mueller RV, Goodson WH. Wound healing. Doherty, Current surgical diagnosis and treatment. Yedinci baskı, 2003:86-99.
24. Grinnell F. Fibroblasts, myofibroblasts, and wound contraction: mini-review on the cellular mechansims of disease. Journal of Cell Biology 1994;124:401-4.
25. Desmoulieri A, Regard M, Darby I, Gabbiani G. Apoptosis mediates the decrease in cellularity during transition between granulation tissue and skar. Am J Pathol. 1995;146:56-66.
26. Costa AM, Peyrol S, Porto LC, Comparin JP, Foyatier JL, Desmoulieri A. Mechanical forces induce scar remodeling: study in non-pressure-treated versus pressure-treated hypertrophic scars. Am J Pathol. 1999;155:1671-9.
27. Çiğremiş Y, Özuğurlu F, Türköz Y, Yüksel E, Gaffuroğlu M, Yılmaz M. Uzun süreli sigara kullanımının eritrosit antioksidan enzim düzeylerine etkisi. SDÜ Fen Bilimileri Enst Derg. 2002;6:184-90.
28. Halliwell B, Gutteridge J. Free radicals in biology and medicine. Üçüncü baskı, Gutteridge Oxford University Press, 1999.
29. Radi R, Rubbo H, Bush K, Freeman BA. Xanthine oxidase binding to glycosaminoglycans: kinetics and superoxide dismutase interactions of immobilized xanthine oxidase-heparin complexes. Arch Biochem Biophys. 1997;339:125-35.
30. Hearse DJ, Manning AS, Downey JM, Yellon DM. Xanthine oxidase: a critical mediator of myocardial injury during ischemia and reperfusion? Acta Physiol Scand. 1986;548:65-78.
31. Fields M, Lewis CG, Lure MD. Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies the signs associated with copper deficiency in rats fed fructose. Free Radical Biol Med. 1996;20:595-600.
32. Vina J, Gimeno A, Sastre J, Desco C, Asensi M, Pallardo FV. Mechanism of free radical production in exhaustive exercise in humans and rats; role of xanthine oxidase and protection by allopurinol. IUBMB Life 2000;49:539-44
33. Sanders SA, Eisenthal R, Harrison R. NADH oxidase activity of human xanthine oxidoreductase–generation of superoxide anion. Eur J Biochem. 1997;245:541-8.
34. Borges F, Fernandez E, Roleira F. Progress towards the discovery of xanthine oxidase inhibitors. Current Medicinal Chemistry 2002;9:195-217.
35. Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature, 1986;320:454-6.
36. http://www.geocities.com/turkerbulut (Bulut T. Özofagus yanıkları)
37. Daly JF, Cardona JC. Corrosive esophagitis. Am J Surg. 1957;93:242-7.
38. Homan CS, Maitra SR, Lane BP, Thode HC, Sable M. Therapeutic effects of water and milk for acute injury of the esophagus. Ann Emerg Med. 1994;24:14-20.
39. Cattan P, Munoz-Bongrad N, Berney T, Halimi B, Sarfati E, Celerier M. Extensive abdominal surgery after caustic ingestions. Ann Surg. 2000;231:519-23.
40. Wijburg FA, Heymans HSA, Urbanus NAM. Caustic esophageal lesions in childhood: prevention of stricture formation. J Pediatr Surg. 1989;24:171-3.
41. Gündoğdu HZ, Tanyel FC, Büyükpamukçu N, Hiçsönmez A. Conservative treatment of caustic esophageal dilatations. J Pediatr Surg. 1992;27:767-70.
42. Demirbilek S, Bernay F, Rızalar R, Barış S, Gürses N. Effects of estradiol and progesterone on the synthesis of collagen in corrosive esophageal burns in rats. J Pediatr Surg. 1994;29:1425-8.
43. Anderson KD, Rouse TM, Randolph JG. Controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med. 1990;10:637-40.
44. Butler C, Madden JW, Davis WM, Peacock EE. Morphologic aspects of experimental esophageal lye strictures. Effect of steroid hormones, bougienage and induced lathyrism on acute lye burns. Surgery 1977;81:431-5.
45. Thompson JN. Corrosive esophageal injuries: a study of nine cases of concurrent accidental caustic ingestion. Laryngoscope 1987;97:1060-8.
46. Baustia A, Tojo R, Varela R, Estevez E, Villanueva A, Canranel S. Effects of prednisolone and dexamethasone on alkali burns of the esophagus in rabbit. J Pediatr Gastroenterol Nutr. 1996;22:275-83.
47. Canranel S, Scaillon M, Goyens P, Rodesch P. Treatment of esophageal caustic injuries: experience with high dose dexamethasone. Pediatr Surg Int. 1993;8:97-102.
48. Çakmak M, Naycı A, Renda N, Erekul S, Gökora H, Yücesan S. The effect of corticosteriods and pentoxifylline in caustic esophageal burns. Int Surg. 1997;82:371-5.
49. Günaydın M, Yıldız L, Rızalar R, Somuncu S, Özdamar Ş, Arıtürk E, Bernay F, Gürses N. Deneysel korozif özofagus yanıklarında intralezyonler uzun etkili kortkosteroid uygulanımının etkisi. Pediatrik Cerrahi Dergisi 1997;11:15-9.
50. Camargo MA, Lopes LR, Grangeia TA, Andreollo NA, Brandalise NA. Use of corticosteroids after esophageal dilations with corrosive stenosis: prospective, randomised and double-blind study. Rev Assoc Med Bras. 2003;49:286-92.
51. Kochhar R, Makharia GK. Usefulness of intralesional triamcinolone in treatment of benign esophageal strictures. Gastrointest Endosc. 2002;56:829-34.
52. Pul M, Yılmaz N, Değer O, Gürses N. Indomethacin for prevention of stricture formation due to alkali-induced corrosive esophageal burns in the rat. Pediatr Surg Int. 1990;5:416-7.
53. Küçükaydın M, Balkanlı S, Yeşilkaya A, Özesmi Ç. Koroziv özofagus striktüründe siklofosfamidin etkisi. Pediatrik Cerrahi Dergisi 1987;2:477-82.
54. Pintus C, Manzoni C, Nappo S, Perelli L. Caustic ingestion in childhood: current treatment possibilities and their complications. Pediatr Surg Int. 1993;8:109-12.
55. Koloğlu MB, Tanyel FC, Müftüoğlu S, Renda N, Çakar N, Büyükpamukçu N, Hiçsönmez A. The preventive effect of heparin on stricture formation after caustic esophageal burns. J Pediatr Surg. 1999;34:291-94.
56. Berthet B, di Costanzo, Arnaud C, Choux R, Assadourian R. Influence of epidermal growth factor and interferon gamma on healing of esophageal corrosive burns in the rat. Br J Surg. 1994;81:395-8.
57. Liu AJ, Richardson MA. Effects n-acetylcysteine of experimentally induced esophageal lye injury. Ann Otol Rhinol Laryngol. 1985;94:477-82.
58. Apaydın BB, Paksoy M, Artış T, Şahin DA, Aki H, Uslu E. Influence of pentoxifylline and interferon-alpha on prevention of stricture due to corrosive esophagitis. Eur Surg Res. 2001;33:225-31.
59. Yükselen V, Karaoğlu A, Yenisey Ç, Tunçyürek M, Özütemiz Ö. Trimetazidine reduces the degree of fibrosis in alkali burns of the esophagus. Journal of Pediatr Surg. (Baskıda).
60. Yükselen V, Karaoğlu A, Özütemiz Ö, Yenisey Ç, Tunçyürek M. Ketotifen ameliorates development of fibrosis in alkali burns of the esophagus. Pediatr Surg Int 2004;20:429-33.
61. Yükselen V, Özütemiz Ö, Vardar E, Oruç N, Yenisey Ç, Postacı H, Karaoğlu A. Özofagusun deneysel alkali yanıklarında infliximabın fibrozis oluşumuna etkisi. 21. Ulusal Gastroenteroloji Haftası, PB:13/8, Antalya, 2004.
62. Kaygusuz I, Çelik O, Özkaya O, Yalçın S, Keleş E, Çetinkaya T. Effects of interferon-alpha-2b and octreotide on healing of esophageal corrosive burns. Laryngoscope 2001;111:199-2004.
63. Yükselen V, Vardar E, Karaoğlu A, Yenisey Ç, Özütemiz Ö. Deneysel koroziv özofagus hasarının tedavisinde kolşisin: eski ilaç, yeni endikasyon? 21. Ulusal Gastroenteroloji Haftası, PB:13/9, Antalya, 2004.
64. Günel E, Çağlayan F, Çağlayan O, Akıllıoğlu İ. Reactive oxygen radical levels in caustic esophageal burns. J Pediatr Surg. 1999;34:405-7.
65. Ulman I, Mutaf O. A critique of systemic steroids in the management of caustic esophageal burns in children. Eur J Pediatr Surg. 1998;8:71-4.
66. Karnak I, Tanyel FC, Büyükpamukçu N, Hiçsönmez A: Combined use of steroid, antibiotics and early bougienage against stricture formation following caustic esophageal burns. J Cardiovasc Surg. 1999;40:307-10.
67. Gandhi RP, Cooper A, Barlow BA. Succesfull management of esophageal strictures without resection or replacement. J Pediatr Surg. 1989;24:745-50.
68. Broto J, Asensio M, Marhuenda C, Gil Vernet JM, Acosta D, Boix Ochoa J. Intraesophageal stent in the prevention of stenosis caused by caustic ingestion. Cir Pediatr. 1999;12:107-9.
69. Naumovski J, Simova N, Janevik-Ivanovska E, Kovkarova E, Georgievksa-Kuzmanovska S. Scintigraphic detection of peptic lesions with the method of radiolabelled sucralfate. Radiol Oncol 2003;37:9-12.
70. Tay HP, Chaparala RC, Harmon JW, Huesken J, Saini N, Hakki FZ, Schweitzer EJ. Bismuth subsalicylate reduces peptic injury of the oesophagus in rabbits. Gut. 1990;31:11-6.
71. Picardi N. Nutritional treatment in the therapeutic strategy in benign esophageal stenosis. Ann Ital Chir. 1992;63:745-54.
72. Mutaf O. Treatment of corrosive esophageal strictures by long-term stenting. J Pediatr Surg. 1996;31:681-5.
73. Mutaf O. Gastroözofageal reflü hastalığı ve özofagus striktürlerinin tedavisi. Pediatrik toraks derneği ilkbahar toplantısı, workshop nisan 2003, izmir.
74. Mutaf O. Esophagoplasty for caustic esophageal burns in children. Pediatr Surg Int. 1992;7:106-8.
75. Gündoğdu HZ, Tanyel FC, Büyükpamukçu N. Colonic replacement for the treatment of caustic esophageal strictures in children. J Pediatr Surg. 1992;27:771.
76. Yararbaş Ö, Osmanoğlu H, Kaplan H, Tokat Y, Çoker A, Korkut M, Kapkaç M. Esophagocoloplasty in the management of postcorrosive strictures of the esophagus. Hepatogastroenterology 1998;45:59-64.
77. Popovici Z. Results of the surgical treatment of severe caustic pharyngeal-esophageal stenosis. The value of complete reconstruction of the pharynx by transposition of the ileum and colon. Chirurgie 1998;123:552-9.
78. http://www.nabi.com/images/prescribinginfo/aloprim%20PI%202003.pdf (AloprimTM – Allopurinol sodium product information)
79. Star VL, Hochberg MC. Prevention and management of gout. Drugs, 1993;45:212-22.
80. Terzi C, Kuzu A, Keşşaf A, Kale T, Tanık A, Köksoy C. Prevention of deleterious effects of reperfusion injury using one-week high-dose allopurinol. Dig Dis Sci. 2001;46:430-7.
81. Gehanno P, Guedon C. Inhibition of experimental esophageal lye strictures by penicillamin. Arch Otolaryngol. 1981;107:145-7.
82. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29:225-9.
83. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.
84. Tietze F. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione. Anal Biochem. 1969;27:502-22.
85. Rangan U, Bulkley GB. Prospects for treatment of free radical-mediated tissue injury. British Medical Bulletin 1993;49:700-18.
86. Das DK, Maulik N. Antioxidant effectiviness in ischemia-reperfusion tissue injury. Methods in Enzymology 1994;233:601-10.
87. Ward PA, Till GO. Pathophysiological events related to the thermal injury os skin. J Trauma 1990;30:575-9 (Suppl 12).
88. Till GO, Guilds LS, Mahrougui KM. Role of xanthine oxidase in thermal injury of skin. Am J Pathol. 1990;135:195-202.
89. Oh TY, Lee JS, Ahn BO, Cho H, Kim YB, Surh YJ, Cho SW, Hahm KB. Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants its treatment. Free Radic Biol Med. 2001;30:905-15.
90. Wetscher GJ, Hinder PR, Bagchi D, Perdikis G, Redmond EJ, Glaser K, Adrian TE, Hinder RA. Free radical scavengers prevent reflux esophagitis in rats. Dig Dis Sci. 1995;40:1292-6.
91. Ridger VC, Pettipher ER, Bryant CE, Brain SD. Effects of the inducible nitric oxide synthase inhibitors aminoguanidine and L-N6-(1-iminoethyl)lysine on zymosan-induced plasma extravasation in rat skin. J Immunol. 1997;159:383-90.
92. Rawlinson A. Nitric oxide, inflammation and acute burn injury. Burns 2003;29:631-40.
93. Chen LW, Hsu CM, Wang JS, Chen HL, Chen JS. Inhibition of inducible nitric oxide synthase (iNOS) prevents lung neutrophil deposition and damage in burned rats. Shock 2001;15:151-6.
94. Garcia NM, Horton JW. Burn injury alters coronary endothelial function. J Surg Res. 1996;60:74-8.
95. Chen LW, Hsu CM, Cha MC, Chen JS, Chen SC. Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure. Shock 1999;11:104-10.
96. Davis KL, Martin E, Turko IV, Murad F. Novel effects of nitric oxide. Annu Rev Pharmacol Toxicol. 2001;41:203-36.
97. Sugiyama S, Norimatsu I, Kobayashi M, Ozawa T, Aoyama H, Suzuki K. Prostaglandins released into human burn blister fluid. Biomedicine 1978;29:51-3.
98. Arturson G. Pathophysiology of the burn wound and pharmalogical treatment: the Rudi Hermans Lecture, 1995. Burns 1996;22:255-74.
99. Grzelak A, Soszynki M, Bartozs G. Inactivation of antioxidant enzymes by peroxynitrite. Scand J Clin Lab Invest. 2000;60:253-8.
100. Gole MD, Souza JM, Choi I, Hertkorn C, Malcolm S, Foust Jr RF. Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2000;278:L961-7.
101. Kawai S, Komura J, Asada Y, Niwa Y. Experimental burn-induced changes in lipid peroxide levels and activity of superoxide dismutase and gluthation peroxidase in skin lesions, serum and liver of mice. Arch Dermatol Res 1988;280:171-5.
102. Epe B, Ballmaier D, Roussyn I, Briviba K, Sies H. DNA damage by peroxynitrite characterised with DNA repair enzymes. Nucleic Acids Res. 1996;24:4105-10.
103. Akçay MN, Özcan O, Gündoğdu C, Akçay G, Balık A, Köse K. Effect of nitric oxide synthase inhibitor on experimentally induced burn wounds. J Trauma 2000;49:327-30.
104. Rizk M, Witte MB, Barbul A. Nitric oxide and wound healing. World J Surg. 2004;28:301-6.
105. Leichus LS, Thomas RM, Murray JA, Conklin JL. Effects of oxygen radicals and radical scavenging on opossum lower esophageal sphincter. Dig Dis Sci. 1997;42:592-6.
106. Dijkstra G, van Goor H, Jansen PL, Moshage H. Targeting nitric oxide in the gastrointestinal tract. Curr Opin Invest Drugs 2004;5:529-36.
107. Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol. 2003;54:469-87.
108. Cheeseman KH. Mechanisms and effects of lipid peroxidation. Molec Aspects Med. 1993;14:191-197.
109. Oh TY, Lee JS, Ahn BO, Cho H, Kim WB, Kim YB, Surh YJ, Cho SW, Lee KM, Hahm KB. Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats. Gut 2001;49:364-71.
110. Czako L, Takacs T, Varga IS, Tiszlavicz L, Hai DQ, Hegyi P, Matkovics B, Lonovics J. Oxidative stress in distant organs and the effect of allopurinol during experimental acute pancreatitis. Int J Pancreatol 2000;27:209-16.
111. Thompson JN. Corrosive esophageal injuries. An investigation of treatment methods and histochemical analysis of esophageal strictures in a new animal model. Laryngoscope 1987;97:1191-202.
112. Reno F, Sabbatini M, Lombardini F, Stella M, Pezzuto C, Magliacani G, Cannas M. In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars. Wound Rep Reg. 2003;11:331-6.
113. Bergeman I, Loxly R. Two improved and simplified methods for spectrophotometric determination of hydroxyproline. Ann Chem 1963;35:1961-5.