PMID- 26614261 OWN - NLM STAT- MEDLINE DCOM- 20161220 LR - 20220321 IS - 1573-2584 (Electronic) IS - 0301-1623 (Linking) VI - 48 IP - 3 DP - 2016 Mar TI - The effects of ozone therapy on caspase pathways, TNF-alpha, and HIF-1alpha in diabetic nephropathy. PG - 441-50 LID - 10.1007/s11255-015-1169-8 [doi] AB - 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-1alpha, and TNF-alpha 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-1alpha, and TNF-alpha 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. CONCLUSION: Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes. FAU - Guclu, Aydin AU - Guclu A AD - Department of Nephrology, Faculty of Medicine, Ahi Evran University, Kirsehir, Turkey. aydinguclu@gmail.com. FAU - Erken, Haydar Ali AU - Erken HA AD - Department of Physiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey. FAU - Erken, Gulten AU - Erken G AD - Department of Physiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey. FAU - Dodurga, Yavuz AU - Dodurga Y AD - Department of Medical Biology, Pamukkale University School of Medicine, Denizli, Turkey. FAU - Yay, Arzu AU - Yay A AD - Department of Histology and Embryology, Erciyes University School of Medicine, Kayseri, Turkey. FAU - Ozcoban, Ozge AU - Ozcoban O AD - Department of Histology and Embryology, Erciyes University School of Medicine, Kayseri, Turkey. FAU - Simsek, Hasan AU - Simsek H AD - Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. FAU - Akcilar, Aydin AU - Akcilar A AD - Experimental Research Unit, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. FAU - Kocak, Fatma Emel AU - Kocak FE AD - Department of Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. LA - eng PT - Journal Article DEP - 20151127 PL - Netherlands TA - Int Urol Nephrol JT - International urology and nephrology JID - 0262521 RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Oxidants, Photochemical) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 66H7ZZK23N (Ozone) RN - EC 3.4.22.- (Caspases) SB - IM MH - Animals MH - Apoptosis MH - Caspases/biosynthesis/*genetics MH - *Diabetes Mellitus, Experimental MH - Diabetic Nephropathies/*genetics/metabolism/therapy MH - *Gene Expression Regulation MH - Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis/*genetics MH - In Situ Nick-End Labeling MH - Male MH - Oxidants, Photochemical/therapeutic use MH - Ozone/*therapeutic use MH - RNA, Messenger/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/biosynthesis/*genetics OTO - NOTNLM OT - Caspase OT - Diabetic nephropathy OT - HIF-1alpha OT - Ozone therapy OT - TNF-alpha EDAT- 2015/11/29 06:00 MHDA- 2016/12/21 06:00 CRDT- 2015/11/29 06:00 PHST- 2015/08/04 00:00 [received] PHST- 2015/11/17 00:00 [accepted] PHST- 2015/11/29 06:00 [entrez] PHST- 2015/11/29 06:00 [pubmed] PHST- 2016/12/21 06:00 [medline] AID - 10.1007/s11255-015-1169-8 [pii] AID - 10.1007/s11255-015-1169-8 [doi] PST - ppublish SO - Int Urol Nephrol. 2016 Mar;48(3):441-50. doi: 10.1007/s11255-015-1169-8. Epub 2015 Nov 27.