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Lung injury aggravated in Streptozotocin-induced diabetes: an experimental study

Year 2022, Volume: 47 Issue: 1, 175 - 182, 31.03.2022
https://doi.org/10.17826/cumj.1020617

Abstract

Purpose: The aim of the study explores the impact and potential mechanisms on the STZ (Streptozotocin)-induced diabetes model histopathologically and immunohistochemically on diabetic lung fibrosis.
Materials and Methods: In this study, 14 adult female Wistar albino rats were divided into groups of seven random animals: the control and STZ induced diabetic groups. In the study, a blood glucose level above 200 mg/dl was accepted as diabetes. Nine days after the experiment, the rats were sacrificed under anesthesia and lung samples were taken from each. The histopathological appearance of the samples was evaluated and histopathologic damage score was performed. Apoptosis and inflammation in tissues were evaluated with caspase-3 and IL-1β immunohistochemically.
Results: In the histopathological examination, the STZ group had a higher histopathologic damage score than the control group, and there were findings such as vascular congestion, thickened alveolar wall, and inflammatory cell infiltration. In the caspase-3 immunohistochemistry, staining of the lung tissues of the STZ group was higher than the control group. This difference was also significant in terms of IL-1β immunoreactivity intensity.
Conclusion: This study determined that lung complications and damage due to diabetes-induced by STZ occurred.

References

  • Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843..
  • Lotfy M, Adeghate J, Kalasz H, Singh J, Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diabetes Rev. 2017;3:3-10.
  • Fontaine-Delaruelle C, Viart-Ferber C, Luyton C, Couraud S. Lung function in patients with diabetes mellitus. Rev Pneumol Clin. 2016;72:10-6.
  • Zou XZ, Gong ZC, Liu T, He F, Zhu TT, Li Dai et al. Involvement of epithelial mesenchymal transition afforded by activation of LOX1/TGF-beta1/KLF6 signaling pathway in diabetic pulmonary fibrosis. Pulm Pharmacol Ther. 2017;44:70-77.
  • Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364:656-65.
  • Wang LM, Zhong NZ, Liu SJ, Zhu XY, Liu YJ. Hypoxia-induced acute lung injury is aggravated in Streptozotocin diabetic mice. Exp Lung Res. 2015; 41:146-54.
  • Johnson DR, O’Connor JC, Hartman ME, Tapping RI, Freund GG. Acute hypoxia activates the neuroimmune system, which diabetes exacerbates. J Neurosci. 2007;27:1161–66.
  • Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016;24:547-53.
  • Sala E, Vived C, Luna J et al. CDK11 promotes cytokine-induced apoptosis in pancreatic beta cells independently of glucose concentration and is regulated by inflammation in the NOD mouse model. Front Immunol. 2021;12:634797.
  • Yilmaz BO, Yildizbayrak N, Aydin Y, Erkan M. Evidence of acrylamide- and glycidamide-induced oxidative stress and apoptosis in Leydig and Sertoli cells. Hum Exp Toxicol. 2017;36:1225-35.
  • Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12:60
  • Zhang HX, Duan GL, Wang CN, Zhang YQ, Zhu XY, Liu YJ. Protective effect of resveratrol against endotoxemia-induced lung injury involves the reduction of oxidative/nitrative stress. Pulm Pharmacol Ther. 2014;27:150-5.
  • Bolkent S, Yanardag R, Bolkent S, Mutlu O. The influence of zinc supplementation on the pancreas of streptozotocin-diabetic rats. Dig Dis Sci. 2019;54:2583-7.
  • Chen CM, Juan SH, Pai MH, Chou HC. Hyperglycemia induces epithelial–mesenchymal transition in the lungs of experimental diabetes mellitus. Acta Histochem. 2018;120:525-33.
  • Xiong XQ, Wang WT, Wang LR, Jin LD, Lin LN. Diabetes increases inflammation and lung injury associated with protectivCe ventilation strategy in mice. Int Immunopharmacol. 2012;13:280-3.
  • Onk D, Onk OA, Erol HS, Ozkaraca M, omaklı S, Ayazoglu TA et al. Effect of melatonin on antioxidant capacity, ınflammation and apoptotic cell death in lung tissue of diabetic rats. Acta Cir Bras. 2018;33:375-85.
  • Chen Y, Zhang F, Wang D, Li L, Si H, Wang C et al. Mesenchymal stem cells attenuate diabetic lung fibrosis via adjusting Sirt3-mediated stress responses in rats. Oxid Med Cell Longev. 2020;2020:8076105.
  • Chen CM, Chou HC, Huang LT. Maternal nicotine exposure induces epithelial- mesenchymal transition in rat offspring lungs. Neonatology. 2015;108:179-87.
  • Oztay F, Sancar-Bas S, Gezginci-Oktayoglu S, Ercin M, Bolkent S. Exendin-4 partly ameliorates-hyperglycemia-mediated tissue damage in lungs of streptozotocin-induced diabetic mice. Peptides, 2018;99:99–107.
  • Sahin Inan ZD, Unver Saraydın S. Evaluation of VEGF, Cytokeratin-19 and caspase 3 immunolocalization in the lung tissue of rat with experimentally induced diabetes. Kafkas Univ Vet Fak Derg. 2019;25:415-420.
  • Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell, 2010;140:805-20.
  • Zheng H, Wu J, Jin Z, Yan L. Potential biochemical mechanisms of lung injury in diabetes. Aging Dis. 2017;8:7-16.
  • Mohamed MZ, Hafez HM, Mohamed HH, Zenhom NM. STAT3 and Nrf2 pathways modulate the protective effect of verapamil on lung injury of diabetic rats. Endocr Regul. 2018;52:192-8.
  • Bas SS, Oktayoglu SG, Bolkent S. Exendin-4 attenuates renal tubular injury by decreasing oxidative stress and inflammation in streptozotocin-induced diabetic mice. Growth Factors. 2015;33:419-29.
  • Conti P, Ronconi G, Caraffa A et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34:327-31.

Streptozotosin kaynaklı diyabette akciğer hasarı: deneysel bir çalışma

Year 2022, Volume: 47 Issue: 1, 175 - 182, 31.03.2022
https://doi.org/10.17826/cumj.1020617

Abstract

Amaç: Bu çalışmanın amacı, diyabetik akciğer fibrozisi üzerine histopatolojik ve immünohistokimyasal olarak STZ (Streptozotosin) kaynaklı diyabet modeli üzerindeki etki ve potansiyel mekanizmaları araştırmaktır.
Gereç ve Yöntem: Bu çalışmada, 14 yetişkin dişi Wistar albino sıçan, 7 rastgele hayvandan oluşan gruplara ayrıldı: kontrol ve STZ ile indüklenen diyabet grupları. Çalışmada kan şekerinin 200 mg/dl'nin üzerinde olması diyabet olarak kabul edildi. Deneyden dokuz gün sonra sıçanlar anestezi altında sakrifiye edildi ve her birinin akciğer örnekleri alındı. Örneklerin histopatolojik görünümleri değerlendirildi ve histopatolojik hasar skoru yapıldı. Dokulardaki apoptoz ve inflamasyon, immünohistokimyasal olarak kaspaz-3 ve IL-1β ile değerlendirildi.
Bulgular: Histopatolojik incelemede STZ grubunun histopatolojik hasar skoru kontrol grubuna göre daha yüksekti ve damar tıkanıklığı, alveol duvarında kalınlaşma, inflamatuar hücre infiltrasyonu gibi bulgular vardı. Kaspaz-3 immünohistokimyasında, STZ grubunda akciğer dokularının boyanması kontrol grubuna göre daha yüksekti. Bu fark, IL-1β immünreaktivite yoğunluğu açısından da anlamlıydı.
Sonuç: Bu çalışmada STZ'ye bağlı olarak pulmoner komplikasyonların ve diyabete bağlı hasarın oluştuğu belirlendi.

References

  • Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843..
  • Lotfy M, Adeghate J, Kalasz H, Singh J, Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diabetes Rev. 2017;3:3-10.
  • Fontaine-Delaruelle C, Viart-Ferber C, Luyton C, Couraud S. Lung function in patients with diabetes mellitus. Rev Pneumol Clin. 2016;72:10-6.
  • Zou XZ, Gong ZC, Liu T, He F, Zhu TT, Li Dai et al. Involvement of epithelial mesenchymal transition afforded by activation of LOX1/TGF-beta1/KLF6 signaling pathway in diabetic pulmonary fibrosis. Pulm Pharmacol Ther. 2017;44:70-77.
  • Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364:656-65.
  • Wang LM, Zhong NZ, Liu SJ, Zhu XY, Liu YJ. Hypoxia-induced acute lung injury is aggravated in Streptozotocin diabetic mice. Exp Lung Res. 2015; 41:146-54.
  • Johnson DR, O’Connor JC, Hartman ME, Tapping RI, Freund GG. Acute hypoxia activates the neuroimmune system, which diabetes exacerbates. J Neurosci. 2007;27:1161–66.
  • Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016;24:547-53.
  • Sala E, Vived C, Luna J et al. CDK11 promotes cytokine-induced apoptosis in pancreatic beta cells independently of glucose concentration and is regulated by inflammation in the NOD mouse model. Front Immunol. 2021;12:634797.
  • Yilmaz BO, Yildizbayrak N, Aydin Y, Erkan M. Evidence of acrylamide- and glycidamide-induced oxidative stress and apoptosis in Leydig and Sertoli cells. Hum Exp Toxicol. 2017;36:1225-35.
  • Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12:60
  • Zhang HX, Duan GL, Wang CN, Zhang YQ, Zhu XY, Liu YJ. Protective effect of resveratrol against endotoxemia-induced lung injury involves the reduction of oxidative/nitrative stress. Pulm Pharmacol Ther. 2014;27:150-5.
  • Bolkent S, Yanardag R, Bolkent S, Mutlu O. The influence of zinc supplementation on the pancreas of streptozotocin-diabetic rats. Dig Dis Sci. 2019;54:2583-7.
  • Chen CM, Juan SH, Pai MH, Chou HC. Hyperglycemia induces epithelial–mesenchymal transition in the lungs of experimental diabetes mellitus. Acta Histochem. 2018;120:525-33.
  • Xiong XQ, Wang WT, Wang LR, Jin LD, Lin LN. Diabetes increases inflammation and lung injury associated with protectivCe ventilation strategy in mice. Int Immunopharmacol. 2012;13:280-3.
  • Onk D, Onk OA, Erol HS, Ozkaraca M, omaklı S, Ayazoglu TA et al. Effect of melatonin on antioxidant capacity, ınflammation and apoptotic cell death in lung tissue of diabetic rats. Acta Cir Bras. 2018;33:375-85.
  • Chen Y, Zhang F, Wang D, Li L, Si H, Wang C et al. Mesenchymal stem cells attenuate diabetic lung fibrosis via adjusting Sirt3-mediated stress responses in rats. Oxid Med Cell Longev. 2020;2020:8076105.
  • Chen CM, Chou HC, Huang LT. Maternal nicotine exposure induces epithelial- mesenchymal transition in rat offspring lungs. Neonatology. 2015;108:179-87.
  • Oztay F, Sancar-Bas S, Gezginci-Oktayoglu S, Ercin M, Bolkent S. Exendin-4 partly ameliorates-hyperglycemia-mediated tissue damage in lungs of streptozotocin-induced diabetic mice. Peptides, 2018;99:99–107.
  • Sahin Inan ZD, Unver Saraydın S. Evaluation of VEGF, Cytokeratin-19 and caspase 3 immunolocalization in the lung tissue of rat with experimentally induced diabetes. Kafkas Univ Vet Fak Derg. 2019;25:415-420.
  • Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell, 2010;140:805-20.
  • Zheng H, Wu J, Jin Z, Yan L. Potential biochemical mechanisms of lung injury in diabetes. Aging Dis. 2017;8:7-16.
  • Mohamed MZ, Hafez HM, Mohamed HH, Zenhom NM. STAT3 and Nrf2 pathways modulate the protective effect of verapamil on lung injury of diabetic rats. Endocr Regul. 2018;52:192-8.
  • Bas SS, Oktayoglu SG, Bolkent S. Exendin-4 attenuates renal tubular injury by decreasing oxidative stress and inflammation in streptozotocin-induced diabetic mice. Growth Factors. 2015;33:419-29.
  • Conti P, Ronconi G, Caraffa A et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34:327-31.
There are 25 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Demet Bolat 0000-0002-3496-1630

Menekşe Ülger 0000-0003-0108-7948

Münevver Baran 0000-0003-0369-1022

Işıl Tuğçe Turan This is me 0000-0002-3127-2207

Arzu Yay 0000-0002-0541-8372

Publication Date March 31, 2022
Acceptance Date January 13, 2022
Published in Issue Year 2022 Volume: 47 Issue: 1

Cite

MLA Bolat, Demet et al. “Lung Injury Aggravated in Streptozotocin-Induced Diabetes: an Experimental Study”. Cukurova Medical Journal, vol. 47, no. 1, 2022, pp. 175-82, doi:10.17826/cumj.1020617.