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Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri

Year 2018, Volume: 2 Issue: 3, 119 - 124, 28.12.2018

İnci Turan , Meryem Ergenç Salih Erdem , Veysel Haktan Özaçmak , Hale Sayan Özaçmak

Abstract

İntestinal iskemi/reperfüyon (İ/R) akciğeri içeren çoklu organ hasarına neden olmaktadır. Pulmoner doku hasarı ve solunum yetmezliği intestinal iskemi sonrası yaygın bir olaydır. Genel olarak serbest oksijen radikalleri (SOR) gibi oksidatif stres mediyatörlerinin İ/R ile oluşan pulmoner hasar gelişiminde rol oynadığına inanılmaktadır. Bu veriler ışığında, bu çalışmanın amacı, metformin tedavisinin sıçanlarda intestinal İ/ R ile indüklenen akut akciğer hasarını azaltıp azaltmayacağını araştırmaktır. İntestinal İ/R’nun sıçan modeli süperiör mezenterik arterin 45 dakika bağlanması sonrasında 3 saatlik reperfüzyonu ile oluşturuldu. Metformin intestinal iskemiden 5 gün önce oral olarak uygulandı (50,100 veya 200mg/kg dozunda). 40 adet Wistar Albino cinsi sıçan 5 gruba ayrıldı: sham konrol, I/R kontrol ve metfornin uygulanan gruplar. Malondialdehid(MDA) ve indirgenmiş glutatyon(GSH) seviyeleri oksidatif stresi değerlendirmek amacıyla ölçüldü. Hasarı gözleyebilmek için doku kesitleri hematoksilen eozin ile boyandı.
Çeşitli dozlarda metformin ön tedavisi yapılan gruplarda tedavi edilmeyen I/R grubu ile karşılaştırıldığında lipid peroksidasyon seviyesinin önemli ölçüde düştüğü tespit edilmiştir. 200mg/kg dozunda metformin ön tedavisi yapılan grupta histopatolojik akciğer hasar skorları diğer gruplarla karşılaştırıldığında anlamlı derecede azalmıştır. Bunlara ek olarak metformin ön tedavisi intestinal İ/R sonrasında akciğer dokusunda GSH seviyelerini normalize etmiştir. Bu çalışmanın sonuçları, metformin ön tedavisinin intestinal İ/R ile oluşan akut akciğer hasarını azaltmanın etkili bir yolu olabileceğini göstermektedir.

Keywords

Metformin intestinal iskemi akut akciğer hasarı oksidatif stres

References

  • 1.Zhao W, Zhou S, Yao W, Gan X, Su G, Yuan D, Hei Z4. Propofol prevents lung injury after intestinal ischemia-reperfusion by inhibiting the interaction between mast cell activation and oxidative stress. Life Sci. 2014;108(2):80-7.
  • 2. Harward TR, Brooks DL, Flynn TC, Seeger JM. Multiple organ dysfunction after mesenteric artery revascularization. J Vasc Surg. 1993;18(3):459-67.
  • 3. Kim K, Li Y,Jin G, Chong W, Liu B, Lu J, Lee K, Demoya M, Velmahos GC, Alam HB. Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion. Resuscitation 2012; 83: 243-248.
  • 4.Huang X, Zhao W, Hu D, Han X, Wang H, Yang J, Xu Y, Li Y, Yao W, Chen C. Resveratrol efficiently improves pulmonary function via stabilizing mast cells in a rat intestinal injury model. Life Sci. 2017; 15:185:30-37
  • 5. Zhang F, Li ZL, Xu XM, Hu Y, Yao JH, Xu W, Jing HR, Wang S, Ning SL, Tian XF. Protective effects of icariin-mediated SIRT1/FOXO3 signaling pathway on intestinal ischemia/reperfusion-induced acute lung injury. Mol Med Rep. 2015; 11(1):269-76.
  • 6.Turan I, Sayan Ozacmak H, Ozacmak VH, Barut F, Ozacmak ID. The effects of S-nitrosoglutathione on intestinal ischemia reperfusion injury and acute lung injury in rats: Roles of oxidative stress and NF-κB. Tissue Cell 2018; 52:35-41.
  • 7. Bayomy NA, Elshafhey SH, ElBakary RH, Abdelaziz EZ. Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: histological, immunohistochemical and biochemical study. Tissue Cell 2014; 46:304-310.
  • 8. Zu G, Guo J, Che N, Zhou T, Zhang X. Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway. Sci Rep. 2016; 6: 38480-34490.
  • 9. Vasileiou I, Kalimeris K, Nomikos T, Xanthopoulou MN, Perrea D, Agrogiannis G, Nakos G, Kostopanagiotou G. Propofol prevents lung injury following intestinal ischemia-reperfusion. J Surg Res. 2012; 172(1):146-52.
  • 10.Karimipour M, Shojaei Zarghani S, Mohajer Milani M, Soraya H. Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats. Bull Emerg Trauma. 2018; 6(2):115-121.
  • 11. Ge XH, Zhu GJ, Geng DQ, Zhang HZ, He JM, Guo AZ, Ma LL, Yu DH. Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats. Physiol Behav. 2017; 170:115-123.
  • 12.El Messaoudi S, Rongen GA, de Boer RA, Riksen NP. The cardioprotective effects of metformin. Curr Opin Lipidol. 2011; 22(6):445-53.
  • 13. Liu Y, Tang G, Zhang Z, Wang Y, Yang GY. Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion. Neurosci Lett. 2014; 579:46–51.
  • 14. El-Mir M-Y, Detaille D, Gloria R, Delgado-Esteban M, Guigas B, Attia S, et al. Neuroprotective role of antidiabetic drug metformin against apoptotic cell death in primary cortical neurons. J Mol Neurosci. 2008; 34(1):77–87.
  • 15. Ashabi G, Khodagholi F, Khalaj L, Goudarzvand M, Nasiri M. Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK/PGC-1α pathway. Metab Brain Dis. 2014; 29(1):47-58.
  • 16. Abd-Elsameea A, Moustaf A, Mohamed A. Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion. Eur Rev Med Pharmacol Sci. 2014;18(16):2387–92.
  • 17. Pirat A, Zeyneloglu P, Aldemir D, Yücel M, Ozen O, Candan S, Arslan G. Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats. Anesth Analg 2006;102(1):225-32. 18.Casini A, Ferrali M, Pampella A, Maellaro E, Comporti M. (1986) Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 123:520 -31.
  • 19. Aykac G, Uysal M, Yalan AS, Kocak-Toker N, Sivas A, Oz H. (1985) The effects of chronic ethanol injection on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicol. 36:71-76.
  • 20. Mo LQ, Chen Y, Song L, Wu GM, Tang N, Zhang YY, Wang XB, Liu KX, Zhou J. Osthole prevents intestinal ischemia-reperfusion-induced lung injury in a rodent model. J Surg Res. 2014; 189(2):285-94.
  • 21. Barut F, Ozacmak VH, Turan I, Sayan-Ozacmak H, Aktunc E. Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats. Clin Invest Med. 2016; 39(1):E15-24.
  • 22. Ghadernezhad N, Khalaj L, Pazoki-Toroudi H, Mirmasoumi M, Ashabi G. Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway. Pharm Biol. 2016; 54(10):2211-9.
  • 23. Cahova M, Palenickova E, Dankova H, Sticova E, Burian M, Drahota Z, Cervinkova Z, Kucera O, Gladkova C, Stopka P, Krizova J, Papackova Z, Oliyarnyk O. Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation. Am J Physiol Gastrointest Liver Physiol. 2015; 309(2):G100-11.
  • 24. Tang G, Yang H, Chen J, Shi M, Ge L, Ge X, Zhu G. Metformin ameliorates sepsis-induced brain injury by inhibiting apoptosis, oxidative stress and neuroinflammation via the PI3K/Akt signaling pathway. Oncotarget 2017; 8(58):97977-97989.
  • 25. Marzi I, Bühren V, Schüttler A, Trentz O. Value of superoxide dismutase for prevention of multiple organ failure after multiple trauma J Trauma 1993; 35: 110-119.
  • 26. Kalimeris K, Briassoulis P, Ntzouvani A, Nomikos T, Papaparaskeva K, Politi A, Batistaki C, Kostopanagiotou G. N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion. J Surg Res. 2016; 206(2):263-272.
  • 27. Yang B, Ni YF, Wang WC, Du HY, Zhang H, Zhang L, Zhang WD, Jiang T. Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2. J Surg Res. 2015; 194(1):273-80.

Year 2018, Volume: 2 Issue: 3, 119 - 124, 28.12.2018

İnci Turan , Meryem Ergenç Salih Erdem , Veysel Haktan Özaçmak , Hale Sayan Özaçmak

Abstract

References

  • 1.Zhao W, Zhou S, Yao W, Gan X, Su G, Yuan D, Hei Z4. Propofol prevents lung injury after intestinal ischemia-reperfusion by inhibiting the interaction between mast cell activation and oxidative stress. Life Sci. 2014;108(2):80-7.
  • 2. Harward TR, Brooks DL, Flynn TC, Seeger JM. Multiple organ dysfunction after mesenteric artery revascularization. J Vasc Surg. 1993;18(3):459-67.
  • 3. Kim K, Li Y,Jin G, Chong W, Liu B, Lu J, Lee K, Demoya M, Velmahos GC, Alam HB. Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion. Resuscitation 2012; 83: 243-248.
  • 4.Huang X, Zhao W, Hu D, Han X, Wang H, Yang J, Xu Y, Li Y, Yao W, Chen C. Resveratrol efficiently improves pulmonary function via stabilizing mast cells in a rat intestinal injury model. Life Sci. 2017; 15:185:30-37
  • 5. Zhang F, Li ZL, Xu XM, Hu Y, Yao JH, Xu W, Jing HR, Wang S, Ning SL, Tian XF. Protective effects of icariin-mediated SIRT1/FOXO3 signaling pathway on intestinal ischemia/reperfusion-induced acute lung injury. Mol Med Rep. 2015; 11(1):269-76.
  • 6.Turan I, Sayan Ozacmak H, Ozacmak VH, Barut F, Ozacmak ID. The effects of S-nitrosoglutathione on intestinal ischemia reperfusion injury and acute lung injury in rats: Roles of oxidative stress and NF-κB. Tissue Cell 2018; 52:35-41.
  • 7. Bayomy NA, Elshafhey SH, ElBakary RH, Abdelaziz EZ. Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: histological, immunohistochemical and biochemical study. Tissue Cell 2014; 46:304-310.
  • 8. Zu G, Guo J, Che N, Zhou T, Zhang X. Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway. Sci Rep. 2016; 6: 38480-34490.
  • 9. Vasileiou I, Kalimeris K, Nomikos T, Xanthopoulou MN, Perrea D, Agrogiannis G, Nakos G, Kostopanagiotou G. Propofol prevents lung injury following intestinal ischemia-reperfusion. J Surg Res. 2012; 172(1):146-52.
  • 10.Karimipour M, Shojaei Zarghani S, Mohajer Milani M, Soraya H. Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats. Bull Emerg Trauma. 2018; 6(2):115-121.
  • 11. Ge XH, Zhu GJ, Geng DQ, Zhang HZ, He JM, Guo AZ, Ma LL, Yu DH. Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats. Physiol Behav. 2017; 170:115-123.
  • 12.El Messaoudi S, Rongen GA, de Boer RA, Riksen NP. The cardioprotective effects of metformin. Curr Opin Lipidol. 2011; 22(6):445-53.
  • 13. Liu Y, Tang G, Zhang Z, Wang Y, Yang GY. Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion. Neurosci Lett. 2014; 579:46–51.
  • 14. El-Mir M-Y, Detaille D, Gloria R, Delgado-Esteban M, Guigas B, Attia S, et al. Neuroprotective role of antidiabetic drug metformin against apoptotic cell death in primary cortical neurons. J Mol Neurosci. 2008; 34(1):77–87.
  • 15. Ashabi G, Khodagholi F, Khalaj L, Goudarzvand M, Nasiri M. Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: interference of AMPK/PGC-1α pathway. Metab Brain Dis. 2014; 29(1):47-58.
  • 16. Abd-Elsameea A, Moustaf A, Mohamed A. Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion. Eur Rev Med Pharmacol Sci. 2014;18(16):2387–92.
  • 17. Pirat A, Zeyneloglu P, Aldemir D, Yücel M, Ozen O, Candan S, Arslan G. Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats. Anesth Analg 2006;102(1):225-32. 18.Casini A, Ferrali M, Pampella A, Maellaro E, Comporti M. (1986) Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 123:520 -31.
  • 19. Aykac G, Uysal M, Yalan AS, Kocak-Toker N, Sivas A, Oz H. (1985) The effects of chronic ethanol injection on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicol. 36:71-76.
  • 20. Mo LQ, Chen Y, Song L, Wu GM, Tang N, Zhang YY, Wang XB, Liu KX, Zhou J. Osthole prevents intestinal ischemia-reperfusion-induced lung injury in a rodent model. J Surg Res. 2014; 189(2):285-94.
  • 21. Barut F, Ozacmak VH, Turan I, Sayan-Ozacmak H, Aktunc E. Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats. Clin Invest Med. 2016; 39(1):E15-24.
  • 22. Ghadernezhad N, Khalaj L, Pazoki-Toroudi H, Mirmasoumi M, Ashabi G. Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway. Pharm Biol. 2016; 54(10):2211-9.
  • 23. Cahova M, Palenickova E, Dankova H, Sticova E, Burian M, Drahota Z, Cervinkova Z, Kucera O, Gladkova C, Stopka P, Krizova J, Papackova Z, Oliyarnyk O. Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation. Am J Physiol Gastrointest Liver Physiol. 2015; 309(2):G100-11.
  • 24. Tang G, Yang H, Chen J, Shi M, Ge L, Ge X, Zhu G. Metformin ameliorates sepsis-induced brain injury by inhibiting apoptosis, oxidative stress and neuroinflammation via the PI3K/Akt signaling pathway. Oncotarget 2017; 8(58):97977-97989.
  • 25. Marzi I, Bühren V, Schüttler A, Trentz O. Value of superoxide dismutase for prevention of multiple organ failure after multiple trauma J Trauma 1993; 35: 110-119.
  • 26. Kalimeris K, Briassoulis P, Ntzouvani A, Nomikos T, Papaparaskeva K, Politi A, Batistaki C, Kostopanagiotou G. N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion. J Surg Res. 2016; 206(2):263-272.
  • 27. Yang B, Ni YF, Wang WC, Du HY, Zhang H, Zhang L, Zhang WD, Jiang T. Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2. J Surg Res. 2015; 194(1):273-80.
There are 26 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Article
Authors

İnci Turan

Meryem Ergenç This is me

Salih Erdem

Veysel Haktan Özaçmak

Hale Sayan Özaçmak

Publication Date December 28, 2018
Acceptance Date December 28, 2018
Published in Issue Year 2018 Volume: 2 Issue: 3

Cite

APA Turan, İ., Ergenç, M., Erdem, S., Özaçmak, V. H., et al. (2018). Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri. Türkiye Diyabet Ve Obezite Dergisi, 2(3), 119-124.
AMA Turan İ, Ergenç M, Erdem S, Özaçmak VH, Sayan Özaçmak H. Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri. Turk J Diab Obes. December 2018;2(3):119-124.
Chicago Turan, İnci, Meryem Ergenç, Salih Erdem, Veysel Haktan Özaçmak, and Hale Sayan Özaçmak. “Sıçanlarda İntestinal İskemi Reperfüzyon Ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri”. Türkiye Diyabet Ve Obezite Dergisi 2, no. 3 (December 2018): 119-24.
EndNote Turan İ, Ergenç M, Erdem S, Özaçmak VH, Sayan Özaçmak H (December 1, 2018) Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri. Türkiye Diyabet ve Obezite Dergisi 2 3 119–124.
IEEE İ. Turan, M. Ergenç, S. Erdem, V. H. Özaçmak, and H. Sayan Özaçmak, “Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri”, Turk J Diab Obes, vol. 2, no. 3, pp. 119–124, 2018.
ISNAD Turan, İnci et al. “Sıçanlarda İntestinal İskemi Reperfüzyon Ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri”. Türkiye Diyabet ve Obezite Dergisi 2/3 (December 2018), 119-124.
JAMA Turan İ, Ergenç M, Erdem S, Özaçmak VH, Sayan Özaçmak H. Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri. Turk J Diab Obes. 2018;2:119–124.
MLA Turan, İnci et al. “Sıçanlarda İntestinal İskemi Reperfüzyon Ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri”. Türkiye Diyabet Ve Obezite Dergisi, vol. 2, no. 3, 2018, pp. 119-24.
Vancouver Turan İ, Ergenç M, Erdem S, Özaçmak VH, Sayan Özaçmak H. Sıçanlarda İntestinal İskemi Reperfüzyon ile Oluşan Akut Akciğer Hasarında Metforminin Koruyucu Etkileri. Turk J Diab Obes. 2018;2(3):119-24.
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Turkish Journal of Diabetes and Obesity (Turk J Diab Obes) is a scientific publication of Zonguldak Bulent Ecevit University Obesity and Diabetes Research and Application Center.

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