Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
International Urology and Nephrology
Published in: International Urology and Nephrology 3/2016

01-03-2016 | Nephrology - Original Paper

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

Authors: Aydın Güçlü, Haydar Ali Erken, Gülten Erken, Yavuz Dodurga, Arzu Yay, Özge Özçoban, Hasan Şimşek, Aydın Akçılar, Fatma Emel Koçak

Published in: International Urology and Nephrology | Issue 3/2016

Login to get access

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.

Conclusion

Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.
Literature
1.
Alberti KGMM, Aschner P, Benet PH (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Report of WHO consultation. Geneva: World Health Organization: part 1; 2–3
2.
Tuttle KR (2005) Linking metabolism and immunology: diabetic nephropathy is an inflammatory disease. J Am Soc Nephrol 16:1537–1538CrossRefPubMed
3.
Mora C, Navarro JF (2006) Inflammation and diabetic nephropathy. Curr Diabetes Rep 6:463–468CrossRef
4.
Su J, Zhou L, Kong X, Yang X, Xiang X, Zhang Y, Li X, Sun L (2013) Endoplasmic reticulum is at the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in the pathogenesis of diabetes mellitus. J Diabetes Res. doi:10.​1155/​2013/​193461
5.
Okouchi M, Okayama N, Aw TY (2009) Preservation of cellular glutathione status and mitochondrial membrane potential by N-acetylcysteine and insulin sensitizers prevent carbonyl stress-induced human brain endothelial cell apoptosis. Curr Neurovasc Res 6:267–278PubMedCentralCrossRefPubMed
6.
Cai L, Li W, Wang G, Guo L, Jiang Y, Kang YJ (2002) Hyperglycemia-induced apoptosis in mouse myocardium—mitochondrial cytochrome c-mediated caspase-3 activation pathway. Diabetes 51:1938–1948CrossRefPubMed
7.
Romeo G, Liu WH, Asnaghi V, Kern TS, Lorenzi M (2002) Activation of nuclear factor-kappa B induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes 51:2241–2248CrossRefPubMed
8.
Ortiz A, Ziyadeh FN (1997) Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Investig Med 45:50–56PubMed
9.
Wolf G, Chen S, Ziyadeh FN (2005) From the periphery of the glomerular capillary wall toward the center of disease. Diabetes 54:1626–1634CrossRefPubMed
10.
Allen DA, Harwood S, Varagunam M, Raftery MJ, Yaqoob MM (2003) High-glucose-induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases. FASEB J 17:908–910PubMed
11.
Wei Z, Ning NL, Jian HX, Zhe LL (2009) HIF-1α expression and retinal cell apoptosis in rat retina ischemia-reperfusion injury. Int J Ophthalmol 2:227–230
12.
Cao ZH, Zheng QY, Li GQ, Hu XB, Feng SL, Xu GL, Zhang KQ (2015) STAT1-mediated down-regulation of bcl-2 expression is involved in IFN-γ/TNF-α-induced apoptosis in NIT-1 Cells. PLoS One 10. doi:10.​1371/​journal.​pone.​0120921
13.
Sagar SK, Zhang C, Guo Q, Yi R, Tang L (2013) Role of expression of endothelin-1 and angiotensin-II and hypoxia-inducible factor-1α in the kidney tissues of patients with diabetic nephropathy. Saudi J Kidney Dis Transpl 24:959–964CrossRefPubMed
14.
Tang L, Yi R, Yang B, Li H, Chen H, Liu Z (2012) Valsartan inhibited HIF-1α pathway and attenuated renal interstitial fibrosis in streptozotocin-diabetic rats. Diabetes Res Clin Pract 97:125–131CrossRefPubMed
15.
Chung CH, Fan J, Lee EY, Kang JS, Lee SJ, Pyagay PE, Khoury CC, Yeo TK, Khayat MF, Wang A, Chen S (2015) Effects of tumor necrosis factor-α on podocyte expression of monocyte chemoattractant protein-1 and in diabetic nephropathy. Nephron Extra 5:1–18PubMedCentralCrossRefPubMed
16.
Fuccio C, Luongo C, Capodanno P, Giordano C, Scafuro MA, Siniscalco D, Lettieri B, Rossi F, Maione S, Berrino L (2009) A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal cortex of neuropathic mice. Eur J Pharmacol 603:42–49CrossRefPubMed
17.
Haj B, Sukhotnik I, Shaoul R, Pollak Y, Coran AG, Bitterman A, Matter I (2014) Effect of ozone on intestinal recovery following intestinal ischemia-reperfusion injury in a rat. Pediatr Surg Int 30:181–188CrossRefPubMed
18.
19.
Erken HA, Genç O, Erken G, Ayada C, Gündoğdu G, Doğan H (2015) Ozone partially prevents diabetic neuropathy in rats. Exp Clin Endocrinol Diabetes 2:101–105
20.
León OS, Menéndez S, Merino N, Castillo R, Sam S, Pérez L, Cruz E, Bocci V (1998) Ozone oxidative preconditioning: a protection against cellular damage by free radicals. Mediators Inflamm 7:289–294PubMedCentralCrossRefPubMed
21.
Yay A, Akkuş D, Yapıslar H, Balcıoglu E, Sonmez MF, Ozdamar S (2014) Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats. Biotech Histochem 89:552–557CrossRefPubMed
22.
Kumar D, Zimpelmann J, Robertson S, Burns KD (2004) Tubular and interstitial cell apoptosis in the streptozotocin-diabetic rat kidney. Nephron Exp Nephrol 96:77–88CrossRef
23.
Wong VY, Keller PM, Nuttall ME, Kikly K, De Wolf WE Jr, Lee D, Ali SM, Nadeau DP, Grygielko ET, Laping NJ, Brooks DP (2001) Role of caspases in human renal proximal tubular epithelial cell apoptosis. Eur J Pharm 433:135–140CrossRef
24.
Liadis N, Murakami K, Eweida M, Elford AR, Sheu L, Gaisano HY, Hakem R, Ohashi PS, Woo M (2005) Caspase-3-dependent β-cell apoptosis in the initiation of autoimmune diabetes mellitus. Mol Cell Bioe 25:3620–3629CrossRef
25.
Ho FM, Liu SH, Liau CS, Huang PJ, Lin-Shiau SY (2000) High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH(2)-terminal kinase and caspase-3. Circulation 101:2618–2624CrossRefPubMed
26.
Koenen TB, Stienstra R, van Tits LJ, de Graaf J, Stalenhoef AF, Joosten LA, Tack CJ, Netea MG (2011) Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1b transcription in human adipose tissue. Diabetes 60:517–552PubMedCentralCrossRefPubMed
27.
Güçlü A, Yonguç N, Dodurga Y, Gündoğdu G, Güçlü Z, Yonguç T, Adıgüzel E, Turkmen K (2015) The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats. Ren Fail 37:192–197CrossRefPubMed
28.
Peralta C, León OS, Xaus C, Prats N, Jalil EC, Planell ES, Puig-Parellada P, Gelpí E, Roselló-Catafau J (1999) Protective effect of ozone treatment on the injury associated with hepatic ischemia-reperfusion: antioxidant-prooxidant balance. Free Radic Res 31:191–196CrossRefPubMed
29.
Al-Dalain SM, Martínez G, Candelario-Jalil E, Menéndez S, Re L, Giuliani A, León OS (2001) Ozone treatment reduces markers of oxidative and endothelial damage in an experimental diabetes model in rats. Pharmacol Res 44:391–396CrossRefPubMed
30.
Martínez-Sánchez G, Al-Dalain SM, Menéndez S, Re L, Giuliani A, Candelario-Jalil E, Alvarez H, Fernández-Montequín JI, León OS (2005) Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol 523:151–161CrossRefPubMed
31.
Candelario-Jalil E, Mohammed-Al-Dalain S, Fernández OS, Menéndez S, Pérez-Davison G, Merino N, Sam S, Ajamieh HH (2001) Oxidative preconditioning affords protection against carbon tetrachloride induced glycogen depletion and oxidative stress in rats. J Appl Toxicol 21:297–301CrossRefPubMed
32.
Kawata K, Iwai A, Muramatsu D (2015) Stimulation of macrophages with the β-glucan produced by aureobasidium pullulans promotes the secretion of tumor necrosis factor-related apoptosis inducing ligand (TRAIL). PLoS One 4. doi:10.​1371/​journal.​pone.​0124809
33.
Xing B, Chen H, Wang L (2015) Ozone oxidative preconditioning protects the rat kidney from reperfusion injury via modulation of the TLR4-NF-κB pathway. Acta Cir Bras 30:60–66CrossRefPubMed
34.
Azuma K, Mori T, Kawamoto K, Kuroda K, Tsuka T, Imagawa T, Osaki T, Itoh F, Minami S, Okamoto Y (2014) Anti-inflammatory effects of ozonated water in an experimental mouse model. Biomed Rep 2:671–674PubMedCentralPubMed
35.
Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshert E (1998) Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485–490CrossRefPubMed
36.
Sun HK, Lee YM, Han KH, Kim HS, Ahn SH, Han SY (2012) Phosphodiesterase inhibitor improves renal tubulointerstitial hypoxia of the diabetic rat kidney. Korean J Intern Med 27:163–170PubMedCentralCrossRefPubMed
37.
Roy S, Sannigrahi S, Majumdar S, Ghosh B, Sarkar B (2011) Resveratrol regulates antioxidant status, inhibits cytokine expression and restricts apoptosis in carbon tetrachloride induced rat hepatic injury. Oxid Med Cell Longev. doi:10.​1155/​703676
38.
Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R, Jha KA, Srinivasan BP (2014) Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats. Exp Eye Res 125:193–202CrossRefPubMed
39.
Suzuki H, Tomida A, Tsuruo T (2001) Dephosphorylated hypoxia inducible factor 1 alpha as a mediator of p53-dependent apoptosis during hypoxia. Oncogene 20:5779–5788CrossRefPubMed
40.
Chang Y, Hsiao G, Chen YC (2007) Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats. Acta Pharmacol Sin 28:327–333CrossRefPubMed
Metadata
Title
The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy
Authors
Aydın Güçlü
Haydar Ali Erken
Gülten Erken
Yavuz Dodurga
Arzu Yay
Özge Özçoban
Hasan Şimşek
Aydın Akçılar
Fatma Emel Koçak
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 3/2016
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-015-1169-8

Other articles of this Issue 3/2016

International Urology and Nephrology 3/2016 Go to the issue

Urology - Original Paper

Clinical characteristics and long-term observation of simple renal cysts in a healthy Korean population

Urology - Review

Is steroids therapy effective in treating phimosis? A meta-analysis

Nephrology - Original Paper

Serum cardiac troponin T and effective blood flow in stable extracorporeal dialysis patients

Urology - Original Paper

Elevated levels of S100A12 in the seminal plasma of infertile men with varicocele

Nephrology - Original Paper

Gender-specific association between metabolic syndrome and decreased glomerular filtration rate in elderly population

Nephrology – Review

New molecular insights in diabetic nephropathy
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits