Redox-Mediated Activation of SIRT1 by Ozone Therapy Attenuates Ucp2 Expression in Experimental Diabetes
Abstract
Oxidative stress contributes to pancreatic β-cell dysfunction and mitochondrial dysregulation in diabetes. Although controlled ozone exposure may activate endogenous antioxidant responses, its relationship with the pancreatic SIRT1–Ucp2 axis remains unclear. This exploratory study investigated whether ozone therapy induces redox adaptation associated with SIRT1 restoration and Ucp2 suppression in streptozotocin (STZ)-induced experimental diabetes. Male Sprague–Dawley rats (n = 28) were randomly assigned to four groups: healthy control (CT), STZ-induced diabetes (45 mg/kg) (STZ), STZ plus oxygen (STZ + O₂), and STZ plus ozone (150 μg/kg/day, intraperitoneally for 7 days) (STZ + O₃). Fasting glucose, insulin, and HOMA-IR were measured. Pancreatic SIRT1 levels were quantified by ELISA, Ucp2 expression was assessed by RT-qPCR, SOD and GPx activities were measured using activity assays, and MDA levels were determined by the TBARS assay. Ozone therapy significantly increased pancreatic SIRT1 levels and suppressed Ucp2 upregulation compared with untreated diabetic rats. These molecular changes were accompanied by increased SOD and GPx activities and reduced MDA levels. However, fasting glucose remained elevated, and HOMA-IR did not significantly improve compared with untreated diabetic rats. These findings suggest that short-term ozone therapy induces pancreatic redox adaptation and modulates the SIRT1–Ucp2 axis in STZ-induced experimental diabetes. Further studies are needed to determine whether longer treatment periods and models with preserved β-cell function can translate these molecular effects into systemic metabolic improvement.
Keywords: diabetes mellitus; insulin resistance; mitochondrial function; oxidative stress; ozone therapy; redox signaling; SIRT1; uncoupling protein 2.
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