BibTex RIS Kaynak Göster

Effects Of Darbepoetin Alpha on Brain Tissue Oxidative Stress in Experimental Ethanol Administration

Yıl 2009, Cilt: 2009 Sayı: 2, 95 - 99, 01.02.2009

Öz

Objectives: The hyperglycosylated erythropoietin analogue darbepoetin alpha (α) has longer half-life and higher in vivo activity. There is no data about the effects of darbepoetin-α on ethanol-induced oxidative stress. In this study, we investigated the effects of darbepoetin-α on brain tissue oxidant/antioxidant status and nitric oxide levels in experimental ethanol administration. Patients and Methods: Forty-four adult male Wistar albino rats were randomly divided into groups: salinetreated group (S) (n=10), saline and darbepoetintreated group (D) (10 μg/kg) (n=10), experimental ethanol-administered [2.5 g/kg (2.6 ml/kg) twice at 2-hr intervals] group (E) (n=12), ethanol-administered and darbepoetin-treated group (ED) (n=12). Results: Malondialdehyde (MDA) levels of ED group were significantly lower than E group (p<0.05). Glutathione (GSH) levels of ED group were significantly higher than E group (p<0.001). NO levels of ED group were significantly lower than E group (p<0.001). Conclusion: We have observed that darbepoetin-α decreases oxidants and increases antioxidants against ethanol-induced oxidative stress. Darbepoetin-α is protective in ethanol-induced organism via its antioxidant activity. Turkish Başlık: Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri Anahtar Kelimeler: Darbepoetin alfa; oksidatif stres; NO; lipit peroksidasyonu Amaç: Eritropoetin analoğu darbepoetin alfa, yarı ömrü uzun ve in vivo yüksek aktiviteye sahip bir moleküldür. Alkolün etkili olduğu organizmada darbepoetinin etkisi henüz ortaya konulmamıştır. Bu çalışmada, deneysel etanol uygulamasında darbepoetin alfanın beyin dokusu oksidan/antioksidan denge ve nitrik oksit seviyesi üzerine etkilerini araştırdık. Hastalar ve Yöntemler: Kırk dört erişkin erkek Wistar Albino sıçan raslantısal olarak gruplara ayrıldı: %0.9 NaCl uygulanan grup (S) (n=10), %0.9 NaCl ve darbepoetin verilen grup (D) (10 μg /kg) (n=10), deneysel etanol uygulaması yapılan [2.5 g/kg (2.6 ml/kg) 2-saatlik aralıklar ile iki defa] grup (E) (n=12), etanol uygulanan ve darbepoetin verilen grup (ED) (n=12). Bulgular: ED grubu malondialdehit (MDA) değerleri E grubundan anlamlı olarak düşüktü (p<0.05). ED grubu glutatyon (GSH) değeri E grubundan anlamlı olarak yüksekti (p<0.001). ED grubu NO değerleri E grubundan anlamlı olarak düşüktü (p<0.001). Sonuç: Deneysel etanol uygulaması modelinde darbepoetin alfanın oksidanları düşürdüğünü, antioksidanları ise artırdığını gözlemledik. Darbepoetin alfa antioksidan aktivitesi ile alkol uygulanan organizmada koruyucu etkilere sahiptir.

Kaynakça

  • Kumral A, Tugyan K, Gonenc S, Genc K, Genc S, Sonmez U, et al. Protective effects of erythropoietin against ethanol-induced apoptotic neurodegenara- tion and oxidative stress in the developing C57BL/6 mouse brain. Brain Res Dev Brain Res 2005;160:146- 56.
  • Masalkar PD, Abhang SA. Oxidative stress and antioxidant status in patients with alcoholic liver disease. Clin Chim Acta 2005;355:61-5.
  • Pushpakiran G, Mahalakshmi K, Anuradha CV. Taurine restores ethanol-induced depletion of antiox- idants and attenuates oxidative stress in rat tissues. Amino Acids 2004;27:91-6.
  • Upadhya SC, Tirumalai PS, Boyd MR, Mori T, Ravindranath V. Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridiza- tion. Arch Biochem Biophys 2000;373:23-34.
  • Oztürk E, Demirbilek S, Köroğlu A, But A, Begeç ZO, Gülec M, et al. Propofol and erythropoietin anti- oxidant properties in rat brain injured tissue. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:81-6.
  • Belayev L, Khoutorova L, Zhao W, Vigdorchik A, Belayev A, Busto R, et al. Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoi- etic protein, in focal cerebral ischemia in rats. Stroke 2005;36:1071-6.
  • Egrie JC, Browne JK. Development and character- ization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 2001;84 Suppl 1:3-10.
  • Jelkmann W. Molecular biology of erythropoietin. Intern Med 2004;43:649-59.
  • Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.
  • Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497-500.
  • Beutler E, Duron O, Kelly Bm. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.
  • Lowry Oh, Rosebrough Nj, Farr Al, Randall Rj. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982;126:131-8.
  • Lieber CS, Leo MA, Aleynik SI, Aleynik MK, DeCarli LM. Polyenylphosphatidylcholine decreases alcohol- induced oxidative stress in the baboon. Alcohol Clin Exp Res 1997;21:375-9.
  • Sun AY, Sun GY. Ethanol and oxidative mechanisms in the brain. J Biomed Sci 2001;8:37-43.
  • Koudelová J, Mourek J. The lipid peroxidation in various parts of the rat brain: effect of age, hypoxia and hyperoxia. Physiol Res 1994;43:169-73.
  • Ghoneim AI, Abdel-Naim AB, Khalifa AE, El-Denshary ES. Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. Pharmacol Res 2002;46:273-9.
  • Kaplowitz N. Mechanisms of liver cell injury. J Hepatol 2000;32:39-47.
  • Nita DA, Nita V, Spulber S, Moldovan M, Popa DP, Zagrean AM, et al. Oxidative damage following cere- bral ischemia depends on reperfusion - a biochemical study in rat. J Cell Mol Med 2001;5:163-70.
  • Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, Sener M, et al. Neuroprotection by resveratrol against traumatic brain injury in rats. Mol Cell Biochem 2007;294:137-44.
  • Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-12.
  • Peunova N, Enikolopov G. Amplification of calcium- induced gene transcription by nitric oxide in neu- ronal cells. Nature 1993;364:450-3.
  • Yamasaki M, Mishima HK, Yamashita H, Kashiwagi K, Murata K, Minamoto A, et al. Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells. Brain Res 2005;1050:15-26.
  • Kubes P, McCafferty DM. Nitric oxide and intestinal inflammation. Am J Med 2000;109:150-8.
  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 1990;87:1620-4.
  • El-Remessy AB, Khalil IE, Matragoon S, Abou- Mohamed G, Tsai NJ, Roon P, et al. Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and can- nabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol 2003;163:1997-2008.
  • Gunasekar PG, Kanthasamy AG, Borowitz JL, Isom GE. NMDA receptor activation produces concur- rent generation of nitric oxide and reactive oxygen species: implication for cell death. J Neurochem 1995;65:2016-21.
  • Hunt NC, Goldin RD. Nitric oxide production by monocytes in alcoholic liver disease. J Hepatol 1992;14:146-50.
  • Baydas G, Tuzcu M. Protective effects of mela- tonin against ethanol-induced reactive gliosis in hip- pocampus and cortex of young and aged rats. Exp Neurol 2005;194:175-81.
  • Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, et al. In vivo evidence that erythropoietin protects neurons from ischemic dam- age. Proc Natl Acad Sci U S A 1998;95:4635-40.
  • Calapai G, Marciano MC, Corica F, Allegra A, Parisi A, Frisina N, et al. Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation. Eur J Pharmacol 2000;401:349-56.
  • Tabira T, Konishi Y, Gallyas F Jr. Neurotrophic effect of hematopoietic cytokines on cholinergic and other neurons in vitro. Int J Dev Neurosci 1995;13:241-52.

Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri

Yıl 2009, Cilt: 2009 Sayı: 2, 95 - 99, 01.02.2009

Öz

Amaç: Eritropoetin analoğu darbepoetin alfa, yarı
ömrü uzun ve in vivo yüksek aktiviteye sahip bir
moleküldür. Alkolün etkili olduğu organizmada darbepoetinin
etkisi henüz ortaya konulmamıştır. Bu
çalışmada, deneysel etanol uygulamasında darbepoetin
alfanın beyin dokusu oksidan/antioksidan
denge ve nitrik oksit seviyesi üzerine etkilerini
araştırdık.
Hastalar ve Yöntemler: Kırk dört erişkin erkek Wistar
Albino sıçan raslantısal olarak gruplara ayrıldı: %0.9
NaCl uygulanan grup (S) (n=10), %0.9 NaCl ve darbepoetin
verilen grup (D) (10 μg /kg) (n=10), deneysel
etanol uygulaması yapılan [2.5 g/kg (2.6 ml/kg) 2-saatlik
aralıklar ile iki defa] grup (E) (n=12), etanol uygulanan
ve darbepoetin verilen grup (ED) (n=12).
Bulgular: ED grubu malondialdehit (MDA) değerleri
E grubundan anlamlı olarak düşüktü (p < 0.05). ED
grubu glutatyon (GSH) değeri E grubundan anlamlı
olarak yüksekti (p < 0.001). ED grubu NO değerleri E
grubundan anlamlı olarak düşüktü (p < 0.001).
Sonuç: Deneysel etanol uygulaması modelinde darbepoetin
alfanın oksidanları düşürdüğünü, antioksidanları
ise artırdığını gözlemledik. Darbepoetin alfa
antioksidan aktivitesi ile alkol uygulanan organizmada
koruyucu etkilere sahiptir.

Kaynakça

  • Kumral A, Tugyan K, Gonenc S, Genc K, Genc S, Sonmez U, et al. Protective effects of erythropoietin against ethanol-induced apoptotic neurodegenara- tion and oxidative stress in the developing C57BL/6 mouse brain. Brain Res Dev Brain Res 2005;160:146- 56.
  • Masalkar PD, Abhang SA. Oxidative stress and antioxidant status in patients with alcoholic liver disease. Clin Chim Acta 2005;355:61-5.
  • Pushpakiran G, Mahalakshmi K, Anuradha CV. Taurine restores ethanol-induced depletion of antiox- idants and attenuates oxidative stress in rat tissues. Amino Acids 2004;27:91-6.
  • Upadhya SC, Tirumalai PS, Boyd MR, Mori T, Ravindranath V. Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridiza- tion. Arch Biochem Biophys 2000;373:23-34.
  • Oztürk E, Demirbilek S, Köroğlu A, But A, Begeç ZO, Gülec M, et al. Propofol and erythropoietin anti- oxidant properties in rat brain injured tissue. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:81-6.
  • Belayev L, Khoutorova L, Zhao W, Vigdorchik A, Belayev A, Busto R, et al. Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoi- etic protein, in focal cerebral ischemia in rats. Stroke 2005;36:1071-6.
  • Egrie JC, Browne JK. Development and character- ization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 2001;84 Suppl 1:3-10.
  • Jelkmann W. Molecular biology of erythropoietin. Intern Med 2004;43:649-59.
  • Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.
  • Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497-500.
  • Beutler E, Duron O, Kelly Bm. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.
  • Lowry Oh, Rosebrough Nj, Farr Al, Randall Rj. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982;126:131-8.
  • Lieber CS, Leo MA, Aleynik SI, Aleynik MK, DeCarli LM. Polyenylphosphatidylcholine decreases alcohol- induced oxidative stress in the baboon. Alcohol Clin Exp Res 1997;21:375-9.
  • Sun AY, Sun GY. Ethanol and oxidative mechanisms in the brain. J Biomed Sci 2001;8:37-43.
  • Koudelová J, Mourek J. The lipid peroxidation in various parts of the rat brain: effect of age, hypoxia and hyperoxia. Physiol Res 1994;43:169-73.
  • Ghoneim AI, Abdel-Naim AB, Khalifa AE, El-Denshary ES. Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. Pharmacol Res 2002;46:273-9.
  • Kaplowitz N. Mechanisms of liver cell injury. J Hepatol 2000;32:39-47.
  • Nita DA, Nita V, Spulber S, Moldovan M, Popa DP, Zagrean AM, et al. Oxidative damage following cere- bral ischemia depends on reperfusion - a biochemical study in rat. J Cell Mol Med 2001;5:163-70.
  • Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, Sener M, et al. Neuroprotection by resveratrol against traumatic brain injury in rats. Mol Cell Biochem 2007;294:137-44.
  • Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-12.
  • Peunova N, Enikolopov G. Amplification of calcium- induced gene transcription by nitric oxide in neu- ronal cells. Nature 1993;364:450-3.
  • Yamasaki M, Mishima HK, Yamashita H, Kashiwagi K, Murata K, Minamoto A, et al. Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells. Brain Res 2005;1050:15-26.
  • Kubes P, McCafferty DM. Nitric oxide and intestinal inflammation. Am J Med 2000;109:150-8.
  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 1990;87:1620-4.
  • El-Remessy AB, Khalil IE, Matragoon S, Abou- Mohamed G, Tsai NJ, Roon P, et al. Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and can- nabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol 2003;163:1997-2008.
  • Gunasekar PG, Kanthasamy AG, Borowitz JL, Isom GE. NMDA receptor activation produces concur- rent generation of nitric oxide and reactive oxygen species: implication for cell death. J Neurochem 1995;65:2016-21.
  • Hunt NC, Goldin RD. Nitric oxide production by monocytes in alcoholic liver disease. J Hepatol 1992;14:146-50.
  • Baydas G, Tuzcu M. Protective effects of mela- tonin against ethanol-induced reactive gliosis in hip- pocampus and cortex of young and aged rats. Exp Neurol 2005;194:175-81.
  • Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, et al. In vivo evidence that erythropoietin protects neurons from ischemic dam- age. Proc Natl Acad Sci U S A 1998;95:4635-40.
  • Calapai G, Marciano MC, Corica F, Allegra A, Parisi A, Frisina N, et al. Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation. Eur J Pharmacol 2000;401:349-56.
  • Tabira T, Konishi Y, Gallyas F Jr. Neurotrophic effect of hematopoietic cytokines on cholinergic and other neurons in vitro. Int J Dev Neurosci 1995;13:241-52.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler
Yazarlar

Pinar Seymen Bu kişi benim

Erman Aytaç Bu kişi benim

Feray Bölükbaşı Bu kişi benim

FATİH Demir Bu kişi benim

Habibe Genç Bu kişi benim

Habibe Genç Bu kişi benim

Hafize Uzun Bu kişi benim

Hafize Uzun Bu kişi benim

Tuncay Altuğ Bu kişi benim

Hakkı Oktay Seymen Bu kişi benim

Hakki Oktay Seymen Bu kişi benim

Yayımlanma Tarihi 1 Şubat 2009
Yayımlandığı Sayı Yıl 2009 Cilt: 2009 Sayı: 2

Kaynak Göster

APA Seymen, P., Aytaç, E., Bölükbaşı, F., Demir, F., vd. (2009). Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri. Balkan Medical Journal, 2009(2), 95-99.
AMA Seymen P, Aytaç E, Bölükbaşı F, Demir F, Genç H, Genç H, Uzun H, Uzun H, Altuğ T, Seymen HO, Seymen HO. Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri. Balkan Medical Journal. Şubat 2009;2009(2):95-99.
Chicago Seymen, Pinar, Erman Aytaç, Feray Bölükbaşı, FATİH Demir, Habibe Genç, Habibe Genç, Hafize Uzun, Hafize Uzun, Tuncay Altuğ, Hakkı Oktay Seymen, ve Hakki Oktay Seymen. “Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri”. Balkan Medical Journal 2009, sy. 2 (Şubat 2009): 95-99.
EndNote Seymen P, Aytaç E, Bölükbaşı F, Demir F, Genç H, Genç H, Uzun H, Uzun H, Altuğ T, Seymen HO, Seymen HO (01 Şubat 2009) Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri. Balkan Medical Journal 2009 2 95–99.
IEEE P. Seymen, “Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri”, Balkan Medical Journal, c. 2009, sy. 2, ss. 95–99, 2009.
ISNAD Seymen, Pinar vd. “Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri”. Balkan Medical Journal 2009/2 (Şubat 2009), 95-99.
JAMA Seymen P, Aytaç E, Bölükbaşı F, Demir F, Genç H, Genç H, Uzun H, Uzun H, Altuğ T, Seymen HO, Seymen HO. Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri. Balkan Medical Journal. 2009;2009:95–99.
MLA Seymen, Pinar vd. “Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri”. Balkan Medical Journal, c. 2009, sy. 2, 2009, ss. 95-99.
Vancouver Seymen P, Aytaç E, Bölükbaşı F, Demir F, Genç H, Genç H, Uzun H, Uzun H, Altuğ T, Seymen HO, Seymen HO. Deneysel Etanol Uygulamasında Darbepoetin Alfanın Beyin Dokusu Oksidatif Stresi Üzerine Etkileri. Balkan Medical Journal. 2009;2009(2):95-9.