Exp Clin Endocrinol Diabetes 2015; 123(02): 101-105
DOI: 10.1055/s-0034-1389954
Article
© Georg Thieme Verlag KG Stuttgart · New York

Ozone Partially Prevents Diabetic Neuropathy in Rats

H. A. Erken
1   Department of Physiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey
,
O. Genç
2   Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
,
G. Erken
1   Department of Physiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey
,
C. Ayada
2   Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
,
G. Gündoğdu
3   Denizli State Hospital, Denizli, Turkey
,
H. Doğan
4   Ozone Treatment Center, Denizli, Turkey
› Author Affiliations
Further Information

Publication History

received 24 June 2014
first decision 13 August 2014

accepted 27 August 2014

Publication Date:
11 December 2014 (online)

Abstract

Neuropathy is one of the most common complications of diabetes mellitus. Although the beneficial effects of good blood glucose control on diabetic neuropathy are known, this control cannot completely prevent the occurrence and progression of diabetic neuropathy. The aim of this study was to investigate whether ozone prevents diabetic neuropathy. 36 adult female Sprague-Dawley rats were randomly divided into 6 groups (n=6): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). Diabetes was induced by a single injection of streptozotocin (60 mg/kg, intraperitoneal [i.p.]), after which insulin was administered (3 IU, i.p.) to the DI and DOI groups for 28 days, and 1.1 mg/kg (50 µg/ml) ozone was given to the O, DO, and DOI groups for 15 days. 4 weeks after the induction of diabetes, the nerve conduction velocity (NCV), amplitude of the compound action potential (CAP), total oxidant status (TOS), and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated. The NCV, amplitude of CAP, and TAS of the DI and DOI groups were higher than those of the D group; the amplitudes of CAP and TAS of the DO group were higher than those of the D group; and the TOS and OSI of the DO, DI, and DOI groups were lower than those of the D group. These findings indicate that ozone partially prevents diabetic neuropathy in rats. It appears that the preventive effects of ozone are mediated through oxidant/antioxidant mechanisms.

 
  • References

  • 1 International Diabetes Federation . The global burden, IDF Diabetes Atlas. 6th ed Brussels, Belgium: International Diabetes Federation; 2013: 29-48 http://www.idf.org/diabetesatlas
  • 2 Tesfaye S, Boulton AJ, Dyck PJ et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010; 33: 2285-2293
  • 3 Hyllienmark L, Alstrand N, Jonsson B et al. Early electrophysiological abnormalities and clinical neuropathy: a prospective study in patients with type 1 diabetes. Diabetes Care 2013; 36: 3187-3194
  • 4 Battino R, Rettich TR, Tominaga T. The solubility of oxygen and ozone in liquids. J Phys Chem Ref Data 1983; 12: 163-178
  • 5 León OS, Menéndez S, Merino N et al. Ozone oxidative preconditioning: a protection against cellular damage by free radicals. Mediators Inflamm 1998; 7: 289-294
  • 6 Peralta C, León OS, Xaus C et al. Protective effect of ozone treatment on the injury associated with hepatic ischemia-reperfusion: antioxidant-prooxidant balance. Free Radic Res 1999; 31: 191-196
  • 7 Hernández F, Menéndez S, Wong R. Decrease of blood cholesterol and stimulation of antioxidative response in cardiopathy patients treated with endovenous ozone therapy. Free Radic Biol Med 1995; 19: 115-119
  • 8 Martínez-Sánchez G, Al-Dalain SM, Menéndez S et al. Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol 2005; 523: 151-161
  • 9 Yagihashi S. Nerve structural defects in diabetic neuropathy: do animals exhibit similar changes?. Neurosci Res Commun 1997; 21: 25-32
  • 10 Biessels GJ, Cristino NA, Rutten GJ et al. Neurophysiological changes in the central and peripheral nervous system of streptozotocin-diabetic rats. Brain 1999; 122: 757-768
  • 11 Leonelli E, Bianchi R, Cavaletti G et al. Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis. Neuroscience 2007; 144: 1293-1304
  • 12 DCCT Research Group . The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med 1995; 122: 561-568
  • 13 Apfel SC, Kessler JA, Adornato BT et al. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology 1998; 51: 695-702
  • 14 Veiga S, Leonelli E, Beelke M et al. Neuroactive steroids prevent peripheral myelin alterations induced by diabetes. Neurosci Lett 2006; 402: 150-153
  • 15 Ido Y, McHowat J, Chang KC et al. Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine. Diabetes 1994; 43: 1469-1477
  • 16 Pitel S, Raccah D, Gerbi A et al. At low doses, a gamma-linolenic acid-lipoic acid conjugate is more effective than docosahexaenoic acid-enriched phospholipids in preventing neuropathy in diabetic rats. J Nutr 2007; 137: 368-372
  • 17 Ziegler D, Low PA, Litchy WJ et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 2011; 34: 2054-2060
  • 18 Pesaresi M, Giatti S, Cavaletti G et al. Sex-dimorphic effects of dehydroepiandrosterone in diabetic neuropathy. Neuroscience 2011; 199: 401-409
  • 19 Roglio I, Bianchi R, Giatti S et al. Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy. Cell Mol Life Sci 2007; 64: 1158-1168
  • 20 Morsy MD, Hassan WN, Zalat SI. Improvement of renal oxidative stress markers after ozone administration in diabetic nephropathy in rats. Diabeteol Metabol Syndr 2010; 2: 29-35
  • 21 Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-1111
  • 22 Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004; 37: 112-119
  • 23 Singhal A, Cheng C, Sun H et al. Near nerve local insulin prevents conduction slowing in experimental diabetes. Brain Res 1997; 763: 209-214
  • 24 Hasegawa O, Matsumoto S, Iino M et al. Interrelationship among nerve conduction velocity, amplitudes of compound muscle and compound nerve action potentials in diabetic neuropathy. No To Shinkei 1999; 51: 863-866
  • 25 Lin Q, Chen H, Lu C et al. Effects of ozone on sciatic nerve in rat. Interv Neuroradiol 2011; 17: 281-285
  • 26 Vincent AM, Russell JW, Low P et al. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev 2004; 25: 612-628
  • 27 Ceretta LB, Réus GZ, Abelaira HM et al. Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats. Exp Diabetes Res 2012; 2012: 1-8
  • 28 Bocci V, Borrelli E, Travagli V et al. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev 2009; 29: 646-682
  • 29 Martín-Gallán P, Carrascosa A, Gussinyé M et al. Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic Biol Med 2003; 34: 1563-1574
  • 30 Serban MG, Negru T. Lipoproteins, lipidic peroxidation and total antioxidant capacity in serum of aged subjects suffering from hyperglycemia. Rom J Intern Med 1998; 36: 65-70
  • 31 Al-Dalain SM, Martínez G, Candelario-Jalil E et al. Ozone treatment reduces markers of oxidative and endothelial damage in an experimental diabetes model in rats. Pharmacol Res 2001; 44: 391-396
  • 32 Candelario-Jalil E, Mohammed-Al-Dalain S, Fernández OS et al. Oxidative preconditioning affords protection against carbon tetrachloride-induced glycogen depletion and oxidative stress in rats. J Appl Toxicol 2001; 21: 297-301
  • 33 Ceriello A, Mercuri F, Quagliano L et al. Detection of nitrotynosive in the diabetic plasma: evidence of oxidative stress. Diabetología 2001; 44: 834-838
  • 34 Fesken EJ, Vintanen SM. Dietary factors determining diabetes and impaired glucose tolerance. A 20-year follow-up of the Finnish and Dutch cohorts of the seven countries study. Diabetes Care 1995; 18: 1104-1112