Metotreksat’ın Neden Olduğu Akut Böbrek Hasarına Karşı Montelukast’ın Etkileri

Amaç: Metotreksat'ın neden olduğu böbrek hasarına karşı montelukast'ın etkileri araştırıldı. Gereç-Yöntem: 35 adet Wistar albino dişi sıçan 5 gruba ayrıldı: Grup I: Kontrol (K); Grup II: Montelukast (ML); Grup III: Metotreksat (Mtx); Grup IV: Önce metotreksat sonra montelukast verilen grup (Mtx+ML); Grup V: Önce montelukast sonra metotreksat uygulanan grup (ML+Mtx) olacak şekilde ayarlandı. Son uygulamalardan 24 saat sonra hayvanlar sakrifiye edilerek böbrek dokuları ve kanları alındı. Böbrek dokuları hem histolojik incelemeler hem de MDA analizi için kullanıldı. Kandan elde edilen serumlarda ise BUN ve Cr seviyeleri değerlendirildi. Bulgular: Sadece metotreksat uygulanan grupta kontrol grubuna gore MDA, BUN ve Cr seviyelerinde anlamlı bir artış tespit edildi. Bunun yanı sıra metotreksat enjeksiyonundan sonra montelukast verilen grupta bu parametreler düşmüştü. Histolojik olarak sadece metotreksat verilen grupta belirgin tübül hasarı varken montelukastın her iki uygulaması ise bu hasarları geriletmişti. Sonuç: Metotreksat'ın neden olduğu deneysel böbrek hasarında, montelukast'ın bu hasarı azalttığı ortaya kondu. Anahtar kelimeler: Metotreksat; Montelukast; Böbrek; Rat.

Anahtar Kelimeler:

Metotreksat; Montelukast; Böbrek; Rat.

The Effects of Montelukast Against Methotrexate-Induced Acute Renal Damage

Objective: The effects of montelukast against methotrexate-induced renal damage were investigated. Materials and Methods: 35 Wistar albino female rats were divided into 5 groups as follows: Group I: Control; Group II: Montelukast (ML); Group III: Methotrexate (Mtx); Group IV: Montelukast treatment after methotrexate application (Mtx+ML); Group V: Montelukast treatment before methotrexate application (ML+Mtx). At the end of the experiment, the kidney tissues and the blood of rats were collected. Malondialdehyde (MDA) levels were determined from kidney tissues. Blood urea nitrogen (BUN) and creatinine (Cr) were assessed in the serum. In addition the kidney tissues were examined histologically. Results: MDA, BUN and Cr levels of of group III significantly increased when compared to groups I and II. These parameters of group IV decreased when comparet to group III. The significant tubul damages were observed in only methotrexate injection group (group III) histologically. In addition, montelukast treatment (in groups IV and V) reduced these histological damages. Conclusion: It was showed that montelukast treatment after methotrexate application could reduce methotrexate-induced experimental renal damage. Key words: Methotrexate; Montelukast; Kidney; Rat.

Keywords:

Methotrexate; Montelukast; Kidney; Rat.,

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Bayram, M, Ozogul C, Dursun A, Ercan ZS, Isik I, Dilekoz E. Light and electron microscope examination of the effects of methotrexate on the endosalpinx. Eur J Obstet Gynecol Reprod Biol 2005; 120: 96-103.
Widemann BC, Balis FM and Kempf-Bielack B et al. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma: incidence, treatment, and outcome. Cancer 2004; 100: 2222-32.
Oktem F, Yilmaz HR, Ozguner F, Olgar S, Ayata A, Uzare E, Uz E. Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester. Toxicol Ind Health 2006; 22(6): 241-7.
Rollino C, Beltrame G, Ferro M, Quattrocchio G, Tonda L, Quarello F. [Cancer treatment-induced nephrotoxicity: BCR-Abl and VEGF inhibitors]. G Ital Nefrol 2010; 27 Suppl 50:S70-4.
Schornagel, J.H. and Mcvie, J.G. The clinical pharmacology of
methotrexate. Cancer Treatment Reviews 1983: 10; 53-7.
Jahovic N, Cevik H and Sehirli AO et al. Melatonin prevents
methotrexate-induced hepatorenal oxidative injury in rats. Journal of Pineal Research 2003; 34: 282 87.
Miyazono Y, Gao F and Horie T. Oxidative stress contributes to
methotrexate-induced small intestinal toxicity in rats. Scandina vian Journal of Gastroenterology 2004; 39: 1119-27.
Cuciureanu M, Caruntu ID, Paduraru O, Stoica B, Jerca L, Crauciuc E, Nechifor M. The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat. Prostaglandins and Other Lipid Mediators 2009; 88: 82-88.
Şener G, Şehirli Ö, Velioğlu-Öğünç A, Çetinel Ş, Gedik N, Caner M, Sakarcan A, Yeğen BÇ. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res 2006; 54: 65- 71.
Damtew B, Marino JA, Fratianne RB, Spagnuolo PJ. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury. J Lab Clin Med 1993; 121: 328-36.
Wallace JL, Beck PL, Morris GP. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? Am J Physiol 1988; 254: 117–23.
Carsin H, Bargues L, Stephanazzi J, Paris A, Aubert P, Le Bever H. Inflammatory reaction and infection in severe burns. Pathol Biol (Paris) 2002; 50: 93-101.
Wallace JL, McKnight GW, Keenan CM, Byles NI, MacNaughton WK. Effects of leukotrienes on susceptibility of the rat stomach to damage and investigation of the mechanism of action. Gastroenterology 1990; 98: 1178-86.
Konturek SJ, Brozozowski T, Drozdowicz D, Beck G. Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet-activating factor and stress in rats. Dig Dis Sci 1988; 33: 806-13.
Sener G, Kabasakal L, Cetinel S, Contuk G, Gedik N, Yeğ en BC. Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs. Burns 2005; 31(5):587-96.
Kabasakal L, Sener G, Cetinel S, Contuk G, Gedik N, Yegen BC. Burn-induced oxidative injury of the gut is ameliorated by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids 2005;72(6): 431-40.
Turtay MG, Firat C, Samdanci E, Oguzturk H, Erbatur S, Colak C. Effects of montelukast on burn wound healing in a rat model. Clin Invest Med. 2010; 1;33(6): E413-21.
Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86:271–8.
Baliga R, Zhang Z, Baliga M, Shah SV. In vitro and in vivo evidence suggesting a role for in cisplatin-induced nephrotoxicity. Kidney Int 1998; 53: 394-401
Sahna E, Parlakpinar H, Cihan OF, Turkoz Y, Acet A. Effects of aminoguanidine against renal ischaemia-reperfusion injury in rats. Cell Biochem Funct 2006; 24: 137-41.
Somi MH, Hajipour B, Abad GD, Hemmati MR, Ghabili K, Khodadadi A, Vatankhah AM. Protective role of lipoic acid on methotrexate induced intestinal damage in rabbit model. Indian J Gastroenterol 2011; 30(1): 38-40.
Sugiyama A, Kimura H, Ogawa S, Yokota K, Takeuchi T. Effects of Polyphenols from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) on Methotrexate-Induced Intestinal Injury in Rats. J Vet Med Sci 2011; 73(5): 673-8.
Heenen M, Laporte M, De Graef C. Methotrexate induces apoptotic cell death in human keratinocytes. Archi Dermatol Res 1988: 290; 240 45.
Lee SM, Koh HJ, Park DC et al. Cytosolic NADP (+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Rad Biol Med 2002: 32; 1185-96.
Sener G, Sakarcan A, Sehirli O, Ekşioğlu-Demiralp E, Sener E, Ercan F, Gedik N, Yeğen BC. Chronic renal failure-induced multiple-organ injury in rats is alleviated by the selective CysLT1 receptor antagonist montelukast. Prostaglandins Other Lipid Mediat 2007; 83: 257-67.