The Possible Role of Medical Ozone in Angiogenesis
Shadia Barakat Barakat
*, Aziza Seif-El Nasr*; Nabil Abdel-Maksoud, Faika El-Ebiary**, Hanaa Amer***, Amal Zaghloul*** & SaharThabet*.
Department of *Physiology & Department of **Histology,
Department of clinical pathology***, Faculty of Medicine, Ainshams
University, Cairo, Egypt; Department of Forensic and Toxicology,
Faculty of Medicine, Cairo University, Egypt.
To elucidate if medical ozone is able to induce angiogenesis, we used three different doses (75,40 &4μg O3/mlO2) in white albino rats by i.p. injection. Angiogenesis was assessed in both skeletal and cardiac muscle at the end of the study using morphometric method. Both capillary density (cap.dens.) & number of muscle fibers per field were counted and the ratio of cap.dens./ m.fib. (C/F) was calculated. The cap. dens. was highest in the large dose group (which was sacrificed after nearly one week due to marked deterioration), but hemolysis was found in all sera, and in the cardiac muscle fibers which showed marked degenerative and hypertrophic changes. The large dose ozone group showed significant rise in WBCs count which was mainly due to lymphocytes increment. This finding was supported by bone marrow examination. Also, both IFN-γ and TNF-α & fibrinogen levels were significantly raised. Significant decrease of platelet count was confirmed by marked decrease in megakaryocytes in the bone marrow of the large ozone dose group.
The moderate dose group that received (40ugO3/mlO2) for four weeks showed hypertrophy and some degenerative changes in the cardiac muscle fibers, together with mononuclear cell infiltration (MNF) around the newly formed capillaries in the soleus muscle.
Also, we found a slight statistically significant rise in cap. density, RBCs count & lymphocytes%, in addition, significant lowering in the 2 plasma fibrinogen was present.TNF-α level was significantly higher, as compared to their controls and the small dose ozone group, but was lower than in the large dose group.
Analysis of C/F ratio in both cardiac and soleus muscle, peripheral blood & bone marrow samples togeher with Malondialdehyde levels (MDA), lactate dehydrogenase (LDH), creatine phosphokinase CPK) and other metabolic parameters are in favor that the best angiogenic response occurred when we lowered the dose markedly to (4μgO3/mlO2) and prolonged the duration of the study to 12 weeks.
Our data collectively are in favor of occurrence of endogenous induction of angiogenesis in both cardiac and skeletal muscle by medical ozone in the three doses used but the smallest dose and longest duration group was the most efficient and physiologic while the largest dose showed toxic signs.