Effects of Ozone Therapy on the Bladder of Rats with Streptozocin-Induced Diabetes

Zeynep Yığman,1,2 Metin Yığman,3 Ayşegül Küçük,4 Deniz Billur,2,5 Ali Doğan Dursun,6 Mustafa Arslan7– 91Department of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara, Türkiye; 2Neuroscience and Neurotechnology Center of Excellence (NÖROM), Gazi University, Ankara, Türkiye; 3Urology Division, Ministry of Health Etlik City Hospital, Ankara, Türkiye; 4Department of Physiology, Medical Faculty, Bandırma Onyedi Eylül University, Bandırma, Türkiye; 5Department of Histology and Embryology, Faculty of Medicine, Ankara University, Ankara, Türkiye; 6Department of Physiology, Faculty of Medicine, Atılım University, Ankara, Türkiye; 7Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara, Türkiye; 8Life Sciences Application and Research Center, Gazi University, Ankara, Türkiye; 9Laboratory Animal Breeding and Experimental Research Center (GÜDAM), Gazi University, Ankara, TürkiyeCorrespondence: Zeynep Yığman, Department of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara, Türkiye, Tel +90 5059067728, Email [email protected]: Diabetes mellitus (DM), an increasingly prevalent condition worldwide, leads to complications in many organs. Diabetic cystopathy is one of the most frequent urological complications impairing the quality of life. Ozone is used therapeutically in various conditions due to its regulatory effects on oxidant status, as well as its microbicidal and immune-modulatory properties. We aimed to determine the effects of ozone on diabetic bladders, focusing on morphological alterations, inflammatory changes, and serum oxidant status.Methods: Twenty-four male Wistar Albino rats were randomly assigned to four groups (n=6 each): control (C), ozone (O), DM, and ozone-administered DM (DM+O). Four weeks after diabetes induction by intraperitoneal streptozotocin injection, O and DM+O rats received daily rectal ozone insufflation for 7 days. At the end of the fifth week, serum samples were collected to evaluate oxidant status, while bladders were analyzed by light and electron microscopy and investigated immunohistochemically for inflammatory cytokines.Results: Compared with the DM group, the DM+O group showed lower serum glucose and TOS levels and higher TAS levels, along with lower OSI values. Histologically, the DM+O group had a higher connective tissue-to-bladder wall ratio, a lower muscle tissue-to-bladder wall ratio, and a lower muscle-to-connective tissue ratio than the DM group. TNF-α and TGF-β immunostaining intensities were lower in the DM+O group compared to the DM group. IL-10 immunostaining intensity was higher in the DM+O group than in the DM group. The thickness of the urothelial basement membrane in the DM+O group was greater than in the DM group.Conclusion: Study findings suggest ozone may limit oxidative stress, inflammation, and structural alterations in the diabetic bladder, indicating a potential supportive role alongside standard diabetes treatment; further studies are needed to confirm its clinical relevance.Keywords: diabetic cystopathy, ozone, oxidative stress, inflammation, urothelium, transmission electron microscopy