Effect of CAPE on Purin Catabolising Enzyme Activities in Bleomycine-Induced Lung Fibrosis

Yıl 2007, Cilt: 12 Sayı: 3, 168 - 172, 01.06.2007

Hüseyin Özyurt Birsen Özyurt Sadık Söğüt Şemsettin Şahin İsmail Temel Ömer Akyol

Öz

Objectives: Pulmonary fibrosis (PF) induced by bleomycin (BLM) is one of the more common side effects encountered during cancer treatment. It has been suggested that the main responsible agent in PF is ROS which are generated also in normal metabolic conditions. In this study, we investigated the preventive or attenuating effects of caffeic acid phenethyl ester that has been demonstrated to have anti-inflammatory, cytocytatic, anticancerogenic, antiprolipherative and antioxidant effects on BLM-induced PF. Material and Methods: Thirty-six rats were divided four groups as sham, BLM, BLM+vitamin E and BLM+CAPE groups. BLM intratracheally, CAPE ve vit E intraperitoneally were administred. At day 14th, lung tissues were removed, xanthine oxidase, adenosine deaminase ve glutathione peroxidase enzymes activity were determined. Results: BLM application to the rats resulted in a significant increase in the XO and ADA activities as compared to the controls. Administration of CAPE and vit E led to the remarkable reduction of XO and ADA activities compared to the rats treated with BLM. There was a decreased in GSH-Px activity in BLM group to the control group. CAPE had a regulator effect on these parameters: the decreased in XO and ADA activities and the increased in GSH-Px activity were seen after CAPE application. Conclusion: We suggest that CAPE is more effective on the prevention of BLM-induced fibrosis via antioxidant and free radical scavenger properties than vit E at the doses used in the present study. CAPE has some attenuating effects PF affecting both oxidant and antioxidant systems as well as purin catabolisation. ©2007, Firat University, Medical Faculty

Anahtar Kelimeler

-

Bleomisin ile Olusturulan Akciğer Fibrozisinde Pürin Katabolizması Enzim Aktiviteleri Üzerine CAPE�nin Etkisi

Öz

Giriş: Antikanserojen etkili bleomisinin (BLM), kanser tedavisi sırasında en sık rastlanan yan etkisinin pulmoner fibrozis (PF) olduğu bilinmektedir. Son yıllarda, PF�den esas sorumlu ajanın, normal metabolik olaylarda üretilen reaktif oksijen türleri olduğu ileri sürülmektedir. Bu deneysel çalışmada, antienflamatuar, sitostatik, antikanserojen, antiproliferatif ve antioksidan etkisi olduğu bilinen CAPE�nin BLM�e bağlı PF�daki önleyici veya hafifletici etkilerinin araştırılması planlandı. Gereç ve Yöntem: 36 adet Sprague�Dawley cinsi sıçan Kontrol, BLM, BLM+ vitamin E (vit E) ve BLM+ CAPE olacak şekilde 4 gruba ayrıldı. BLM (7.5 mg/kg, tek doz) intratrakeal, CAPE ve vit E intraperitoneal olarak uygulandı. 14. günde akciğer dokuları çıkarıldı, ksantin oksidaz (XO), adenozin deaminaz (ADA) ve glutatyon peroksidaz (GSH-Px) enzim aktiviteleri çalışıldı. Bulgular: BLM uygulanan sıçanlarda, XO ve ADA enzim aktivitelerinde kontrol grubuna göre anlamlı artış vardı. CAPE ve E vit uygulanması ile bu iki enzim aktiviteleri özellikle BLM alan gruba göre anlamlı bir azalma gösterdi. Antioksidan enzim olan GSH-Px enzim aktivitesinde BLM verilen grupta kontrol grubuna göre anlamlı bir azalma vardı. CAPE�nin bu parametreler üzerine düzenleyici etkileri: CAPE uygulandıktan sonra XO ve ADA enzim aktivitelerinde azalma, GSH-Px enzim aktivitesinde artma şeklindedir. Sonuç: BLM�e bağlı PF�in önlenmesinde antioksidan veya serbest radikal süpürücü etki olarak kullanılan dozlarda CAPE, E vit den daha etkilidir. CAPE, pürin katabolizması yanında hem oksidan hem de antioksidan sistemleri etkileyerek BLM�e bağlı PF üzerinde iyileştirici etkiye sahiptir. ©2007, Fırat Üniversitesi, Tıp Fakültesi

Anahtar Kelimeler

Ksantin oksidaz, Adenozin deaminaz, Glutatyon peroksidaz, Bleomisin, Sıçan

Kaynakça

• Ommaty R: Vademecum modern ilaç rehberi. 24. baskı, 2002.
• Sausville EA, Stein RW, Peisach J, Horwitz SB.: Properties and products of the degradation of DNA by bleomycin and iron(II). Biochemistry. 1978; 17: 2746-2754.
• Zitnik RJ.: Drug-induced lung disease: cancer chemotherapy agents. J Respir Dis. 1995; 16: 855-865.
• Cunningham ML, Ringrose PS, Lokesh BR.: İnhibition of the genotoxicity of bleomycin by superoxide dismutase. Mutat Res 1984; 135: 199-202.
• Sausville EA, Stein RW, Peisach J, Horwitz SB.: Properties and products of the degradation of DNA by bleomycin and iron(II). Biochem 1978; 17: 2746-2754.
• Amoros M, Lurton E, Boustie J, Girre L, Sauvager F, Cormier M.: Comparison of the anti-herpes simplex virus activities of propolis and 3-methyl-but-2-enyl caffeate. J Nat Prod 1994; 57:644-647
• Amoros M, Sauvager F, Girre L, Cormier M.: In vitro antiviral activity of propolis. Apidologie 1992; 23:231-240.
• Dobrowolski JW, Vohoraq SB, Sharma K, Shah SA, Naqvi SA, Dandiya antiinflammatory, and antipyretic studies on propolis bee products. J Ethnopharmacol 1991; 35:77-82. antifungal, antiamoebic, 9. Dimov V, Ivanovska N, Bankova V, Popov S.: Immunomodulatory action of propolis: IV. Prophylactic activity against gram-negative infections and adjuvant effect of the water- soluble derivate. Vaccine 1992; 10: 817-823.
• Pascual C, Gonzales R, Torricella RG.: Scavenging action of propolis extract against oxygen radicals. J Ethnopharmacol 1994; 41:9-13.
• Krol W. Czuba Z, Scheller S, Gabrys J, Grabiec S, Shani J.: Anti- oxidant property of etanolic extract of propolis (EEP) evaluated by inhibiting the chemiluminescence oxidation of luminol. Biochem Int 1990; 21:593-597.
• Volpert R, Elstner EF.: Biochemical activities of propolis extracts: II. Photodynamic activities. Z Naturforsch 1993; 48:858-862.
• Edenharder R, von Petersdorff I, Rauscher R.: Antimutagenic effectsof flavanoids, chalcones and structurally related compounds on the activity of 2-amino- 3 methylimidazol (4,5-f) quinoline (IQ) and other heterocyclic amine mutagens from cooked food. Mutat Res 1993; 287:261-274.
• Ozyurt H, Sogut S, Yildirim Z ve ark.: Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung fibrosis in rats. Clin Chim Acta. 2004; 339:65-75. 15.
• Prajda N, Weber G.: Malign transformation-linked imbalance: decresed XO activity in hepatomas. FEBS Lett 1995; 59:245-249.
• Giusti G.: Adenosine deaminase. In: Methods of Enzymatic Analysis (Ed., Bergmeyer MV), pp 1092-1098, 2nd ed. New York: Academic Press, 1974.
• Paglia DE, Valentine WN.: Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab & Clin Med 1967; 70:158-169.
• Rahman I, MacNee W.: Lung glutathione and oxidative stress:Implications in cigarette smoke-induced airways disease. Am J Physiol 1999; 277:1067-1088.
• Rahman I, MacNee W.: Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radical & Biology 2000; 28:1405-1420.
• Sogut S, Ozyurt H, Armutcu F ve ark.: Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats. Eur J Pharmacol. 2004; 494:213-220.
• Quinlan GJ, Lamb NJ, Tilley R, Evans TW, Gutteridge JM.: Plasma hypoxanthine levels in ARDS: implications for oxidative stress, morbidity, and mortality. Am J Respir Crit Care Med 1997; 155: 479–484.
• McCord JM.: Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985; 312: 159–163.
• Granger DN, Hollwarth ME, Parks DA.: Ischemia–reperfusion injury: role of oxygen-derived free radicals. Acta Physiol Scand 1986; 548(Suppl.): 47–63.
• Grum CM, Ragsdale RA, Ketai LH, Simon RH.: Plasma xanthine oxidase activity in patients with adult respiratory distress syndrome. J Crit Care 1987; 2: 22–26.
• Ozyurt H, Irmak MK, Akyol O, Sogut S. Caffeic acid phenethyl ester changes the indices of oxidative stress in serum of rats with renal ischemia–reperfusion injury. Cell Biochem Funct 2001; 19: 259–263.
• Ilhan A, Koltuksuz U, Ozen S, Efkan U, Ciralik H, Akyol O.: The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothor Surg 1999; 16: 458–463.
• Irmak MK, Koltuksuz U, Kutlu NO ve ark.: The effect of caffeic acid phenethyl ester on ischemia–reperfusion injury in comparision with alpha-tocopherol in rat kidneys. Urol Res 2001; 29: 190–193.
• Yildirim Z, Hasanoglu HC, Akyol O, Gokirmak M, Koksal N.: Serum adenosine deaminase activities in lung cancer and mesothelioma. Clin Biochem 1999; 32: 283–285.
• Akyol O, Gokbulut I, Koksal N, Akin H, Ozyurt H, Yildirim Z.: The activities of purine catabolizing enzymes in plasma and bronchial washing fluid in patients with lung cancer and pneumonia. Clin Biochem 2001; 34: 251–254.
• Kabul Tarihi: 23.08.2006