טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentTelerman Alona
SubjectPossible Involvement of Free Radicals in the Pathogenesis of
Obstructive Sleep Apnea Syndrome (OSAS)
DepartmentDepartment of Medicine
Supervisor Dr. Lena Lavie


Abstract

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated apnea-related hypoxemic events during sleep that similarly to ischemia/reperfusion injury, initiate oxidative stress and increase free-radical production. Apnea-induced free-radical generation increases oxidative stress and plasma-lipid peroxidation, which may exacerbate atherogenic processes in OSAS patients. Two lipid peroxidation biomarkers were studied, thio-barbituric acid reactive substances (TBARS) and  lipid peroxides and the antioxidant protective enzyme paraoxonase-1 (PON1). These   were measured in OSAS patients with and without cardiovascular diseases (Only OSAS and CV+HTN OSAS) and in OSAS patients after treatment with nasal Continous Positive Airway Pressure (nCPAP) treatment, in comparison with non-apneic controls. Several of the plasma samples were also investigated by thermochemiluminescence assay (TCL), which measures the oxidizability of plasma. Morning concentrations of TBARS and peroxides were significantly higher in Only OSAS and CV+HTN OSAS patients than in controls (p<.0001). PON1 was lower in CV+HT OSAS than in controls (p<.0004) and in Only OSAS (p<.025). After a single titration night for nCPAP, there was a significant decrease in TBARS (p<.0004) and peroxides (p<.01), while PON1 activity was significantly increased (p<.01). After 9.2±3.19 months of effective nCPAP treatment, TBARS and peroxides levels were lowered to values similar to controls levels. Both, TBARS and peroxides significantly increased with increasing respiratory disturbance index (RDI) (TBARS: r=.47, p<.001; peroxides: r=.39, p<.002), while PON1 was inversely correlated (r= -.47, p<.001). TCL assay corroborated these findings by showing that the plasma of OSAS patients had a higher oxidizability than in controls (p<.017).

Taken together, the increase in lipid peroxidation biomarkers and the decreased PON1 activity on one hand and on the other, the decreased  lipid peroxidation and increased PON1 activity observed after effective nCPAP treatment support the existence of oxidative stress and its possible involvement in cardiovascular morbidity in OSAS patients.