title: The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.
authors.affiliation: Department of Nephrology, Faculty of Medicine, Ahi Evran University, Kırşehir, Turkey. aydinguclu@gmail.com.
authors.forename: Aydın
authors.initials: A
authors.lastname: Güçlü
authors.affiliation: Department of Physiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey.
authors.forename: Haydar Ali
authors.initials: HA
authors.lastname: Erken
authors.affiliation: Department of Physiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey.
authors.forename: Gülten
authors.initials: G
authors.lastname: Erken
authors.affiliation: Department of Medical Biology, Pamukkale University School of Medicine, Denizli, Turkey.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Dodurga
authors.affiliation: Department of Histology and Embryology, Erciyes University School of Medicine, Kayseri, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Yay
authors.affiliation: Department of Histology and Embryology, Erciyes University School of Medicine, Kayseri, Turkey.
authors.forename: Özge
authors.initials: Ö
authors.lastname: Özçoban
authors.affiliation: Department of Physiology, Faculty of Medicine, Dumlupınar University, Kutahya, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Şimşek
authors.affiliation: Experimental Research Unit, Faculty of Medicine, Dumlupınar University, Kutahya, Turkey.
authors.forename: Aydın
authors.initials: A
authors.lastname: Akçılar
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Dumlupınar University, Kutahya, Turkey.
authors.forename: Fatma Emel
authors.initials: FE
authors.lastname: Koçak
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D008297:Male; D010083:Oxidants, Photochemical / Q000627:therapeutic use; D010126:Ozone / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone; D020169:Caspases
keywords: Caspase; Diabetic nephropathy; HIF-1α; Ozone therapy; TNF-α