ناقشت بنجاح طالبة الماجستير
رويدا بنيان من قسم الصيدلة السريرية يوم الأحد 16/8/2015م بعنوان:
Evaluation of the role of spironolactone on
myocardial oxidative stress in rat model of streptozotocin-induced diabetes
وقد ضمت لجنة المناقشة الدكتورة فاديا مياس
رئيسا وعضوية كل من الدكتور كارم الزعبي والدكتور محمد خطاطبه والدكتور عمر قموه
كممتحن خارجي.
باسم صفحة أصدقاء كلية الصيدلة_ في جامعة العلوم
والتكنولوجيا الأردنية نبارك للطالبة رويدا بنيان إتمامها درجة الماجستير في
الصيدلة السريرية بنجاح متمنين لها مزيدا من التقدم والنجاح.
* للاطلاع على ملخص الدراسة:
Background: Diabetes mellitus is a common chronic disease
that has been linked to the development and progression of heart failure and
other cardiovascular diseases (CVDs). Several mechanisms may contribute to the
substrates of CVDs during diabetes such as inflammation, impaired hormonal
regulation and oxidative stress. Recently, oxidative stress has gained
attention as a key player. Oxidative stress is determined by the imbalance
between the generation of reactive oxygen species (ROSs) and the antioxidant
defenses in the body. ROSs generation promotes cellular dysfunction and damage
by sequence of inflammatory, structural and apoptotic processes. The rennin
angiotensin aldosterone system (RAAS) is involved in the pathophysiology of
CVDs. Aldosterone is an adrenal hormone, and a critical modulator of blood
pressure and electrolytes balance. Aldosterone contributes to cardiac
inflammation, oxidative stress, and remodeling. The angiotensin converting
enzyme inhibitors or receptor antagonists are key cardio and reno-protective
medications for patients with DM and underlying CVDs. Spironolactone, an
aldosterone antagonist, has been also shown to improve cardiac function and to
attenuate cardiac remodeling. The impact of aldosterone antagonist on
myocardial oxidative status in DM is unclear
Aim: To evaluate short term impact of
streptozotocin induced DM (single injection 35mg/Kg) on myocardial aldosterone
levels, ROSs, and oxidative stress markers, and to determine the effects of
four weeks treatment with spironolactone on myocardial ROSs levels, and
oxidants/antioxidants markers in diabetic rat model
Method: Young adult Sprague Dawley rats weighing
(245-340 g) were randomly assigned into four groups (12-15 each); normal rats
(control), normal rats treated with 50 mg/kg spironolactone (Spir), diabetic
rats (DM), and diabetic rats treated with 50 mg/kg spironolactone (DM+Spir) for
4 weeks. Body weight and blood glucose were measured at baseline and throughout
the study. Blood pressure was measured at base line and at the end of the
study. At the terminal day, blood samples were collected to measure serum
lipids, glycated hemoglobin (HbA1c) and glucose levels. Cardiac tissues were
homogenized for measurements of aldosterone levels and oxidants/ antioxidants
markers
Result: The use of STZ induced DM and increased the
percentage of HbA1c, but did not cause dyslipidemia, hypertension or cardiac
dilation in both spironolactone treated and untreated rats. Relative to
control, a significant increase in aldosterone levels was observed in the DM
and DM+Spir groups. This increase was paralleled with a significant increase in
total nitrite levels (ROSs form) and a significant reduction in vitamin E antioxidant levels in the DM group. Use of
spironolactone reduced total nitrite levels and improved vitamin E cardiac
levels. A significant increase in glutathione reductase / peroxidase activities
was observed in the DM and DM+Spir groups without changes in the ratio of
reduced to oxidized form of glutathione (GSH/GSSG). Relative to control, a
significant increase in superoxide dismutase (SOD) and catalase activities was
observed in the DM group. Cardiac lipid peroxidation products (TBARS) were
similar among the groups
Conclusions: Our study suggests that STZ induced-DM is
associated with increased myocardial aldosterone levels and total nitrite (ROSs
form) formation. Use of spironolactone reduced nitrite generation and improved
vitamin E antioxidant levels independent of blood pressure lowering effect. The
increase in total nitrite in DM promoted significant compensatory increases in
enzyme antioxidant activities of SOD, catalase and GSH peroxidase/reducatase
probably to reduce excessive ROSs generation and to prevent cardiac oxidative
damage as observed by the lack of cardiac changes in TBARS and GSH/GSSG levels
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