Ozone Therapy Diabetes Mellitus
Ozone Therapy Effects in the Oxidative Stress Associated to Diabetes Mellitus
Saied M. Al-Dalien1, Silvia Menéndez2, Gregorio Martínez1, José I. Fernández-Montequín3,
Eduardo J. Candelario1 and Olga S. León1*
1Center for Research and Biological Evaluation, University of Havana, Institute of Pharmacy
and Food Sciences. Apartado Postal 6079, Havana City 10600, Cuba
2 Ozone Research Center, National Center for Scientific Research. Apartado Postal 6880,
Havana City, Cuba
3 Institute of Angiology and Vascular Surgery. Calzada del Cerro 1551 Cerro. Havana City,
It is well recognized the presence of oxidative stress in diabetes mellitus. Ozone can exert its protective effects by means of an oxidative preconditioning, stimulating and/or preserving the endogenous antioxidant systems. The aim of this paper is to evaluate the ozone effects, in a preclinical and preliminary clinical studies, in the oxidative stress associated to diabetes. Rats were divided in: 1-negative control group; 2- positive, using streptozotocin (STZ) as a diabetes inductor; 3- ozone, 10 treatments (1 mg kg-1), after STZ-induced diabetes and 4-oxygen (26 mg kg-1), as group 3 but using oxygen. Patients with diabetic foot were divided in 2 groups: ozone (using rectal and local ozone) and antibiotic (systemic and locally). Ozone treatment improved glycemic control and prevented oxidative stress associated to diabetes mellitus and its complications, in both studies, in agreement with the excellent results obtained clinically.
Diabetes mellitus is characterized by metabolic abnormalities, a disorder of carbohydrate metabolism, with the presence of hyperglycemia and glycosuria, resulting from inadequate production or utilization of insulin. Long-term complications, that cause morbidity and premature mortality, is characterized by microvascular disease with capillary basement membrane thickening, macrovascular disease with accelerated atherosclerosis, neuropathy involving both the somatic and autonomic nervous systems, neuromuscular dysfunction with muscle wasting, embryopathy and decrease resistance to infections. Such chronic complications involve the eyes, kidneys, heart, nerves and blood vessels. Accelerated atherosclerosis produces 80 % of all diabetic mortality, three fourths off it owing to coronary disease. A more frequent concomitant of distal anesthesia is the development of neurotropic ulceration, particularly on the plantar aspect of the foot. Anesthesia leads to a worsening of any minor injury because of the absence of protective painful stimuli. This problem in addition to pre-existing microvascular and macrovascular circulatory impairments characterizes the underlying mechanisms that may lead to rapid gangrene after foot injury (1,2).
It has been demonstrated, in diabetic patients, the role of the reactive oxygen species (ROS) with an increase oxidative damage at the level of lipid peroxidation, DNA injury and protein damage (3-5). Activation of polyol pathway, non-enzymatic glycosylation of proteins and the increase of ROS play an important role in diabetes complications (6,7). Also, a decrease in the antioxidant defense system, involving the erythrocyte superoxide dismutase and catalase (8,9), with a simultaneous decrease in vitamin C concentration in leukocytes (10) and a decrease in the scavenger capacity of radicals in plasma have been mentioned (11).
Ozone can exert its protective effects by means of an oxidative preconditioning, stimulating and/or preserving the endogenous antioxidant systems and by blocking the xanthine/xanthine oxidase pathway for ROS generation, as it has been demonstrated in the damage induced by carbon tetrachloride (CCl4) and in the hepatic and renal ischemia-reperfusion (12-15). Also, ozone oxidative preconditioning has been proven to preserve glycogen content and to reduce lactate and uric acid formation, controlling oxidative stress induced by CCl4 administration to rats (16). In addition, it has been demonstrated that endovenous ozone therapy, in patients with myocardial infarction, has a beneficial effect on blood lipid metabolism, decreasing blood cholesterol and provoking the activation of antioxidant protection system (17). Ozone has been used with good results in the treatment of patients with diabetic foot, taking into account its germicide properties and its influence in the processes of oxygen metabolization, besides other effects (18).
The socioeconomic impact of diabetes is devastating to individual patients and society as a whole. Any treatment that is capable to normalize oxygen metabolism, to modulate the oxidative stress and to have germicide properties can improve the quality of life of these patients, as well as diminish patient consumption of medicines. Taking into account the ozone therapeutical properties, the aim of this study is to evaluate the ozone effects in the oxidative stress associated to diabetes mellitus, using a preclinical and a preliminary clinical studies.