International Urology and Nephrology

, Volume 48, Issue 3, pp 441–450 | Cite as

The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy

  • Aydın GüçlüEmail author
  • Haydar Ali Erken
  • Gülten Erken
  • Yavuz Dodurga
  • Arzu Yay
  • Özge Özçoban
  • Hasan Şimşek
  • Aydın Akçılar
  • Fatma Emel Koçak
Nephrology - Original Paper



Accelerated apoptosis plays a vital role in the development of diabetic vascular complications. Ozone may attenuate diabetic nephropathy by means of decreased apoptosis-related genes. The aim of our study was to investigate the effect of ozone therapy on streptozotocin-induced diabetic nephropathy in rats. Also the histopathological changes in diabetic kidney tissue with ozone treatment were evaluated.


The rats were randomly divided into six groups (n = 7): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). D, DI, and DOI groups were induced by a single intraperitoneal injection of streptozotocin. Ozone was given to the O, DO, and DOI groups. Group DI and DOI received subcutaneous (SC) insulin (3 IU). All animals received daily treatment for 6 weeks.


Expressions of caspase-1-3-9, HIF-1α, and TNF-α genes were significantly higher in D group compared to C group (p < 0.05 for all). Ozone treatment resulted in significant decrease in the expressions of these genes in diabetic kidney tissue compared to both C and D group (p < 0.05 for all). Caspase-1-3-9, HIF-1α, and TNF-α gene expressions were found to be lower in DOI group compared to C group (p < 0.05 for all). Also adding ozone treatment to insulin therapy resulted in more significantly decrease in the expressions of these genes in diabetic tissue compared to only insulin-treated diabetic group (p < 0.05 for all). Regarding histological changes, ozone treatment resulted in decrease in the renal corpuscular inflammation and normal kidney morphology was observed. Both insulin and ozone therapies apparently improved kidney histological findings with less degenerated tubules and less inflammation of renal corpuscle compared to D, DO, and DI groups.


Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.


Diabetic nephropathy Ozone therapy Caspase HIF-1α TNF-α 


Compliance with ethical standards

Conflict of interest


Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All experimental protocols conducted on the animals were consistent with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (NIH Publication No: 85-23) and approved by the Local Ethical Committee.


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Aydın Güçlü
    • 1
    Email author
  • Haydar Ali Erken
    • 2
  • Gülten Erken
    • 2
  • Yavuz Dodurga
    • 3
  • Arzu Yay
    • 4
  • Özge Özçoban
    • 4
  • Hasan Şimşek
    • 5
  • Aydın Akçılar
    • 6
  • Fatma Emel Koçak
    • 7
  1. 1.Department of Nephrology, Faculty of MedicineAhi Evran UniversityKırşehirTurkey
  2. 2.Department of Physiology, Faculty of MedicineBalikesir UniversityBalikesirTurkey
  3. 3.Department of Medical BiologyPamukkale University School of MedicineDenizliTurkey
  4. 4.Department of Histology and EmbryologyErciyes University School of MedicineKayseriTurkey
  5. 5.Department of Physiology, Faculty of MedicineDumlupınar UniversityKutahyaTurkey
  6. 6.Experimental Research Unit, Faculty of MedicineDumlupınar UniversityKutahyaTurkey
  7. 7.Department of Biochemistry, Faculty of MedicineDumlupınar UniversityKutahyaTurkey

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