الفهرس 
Title : Cardioprotective Effect Of Valsartan Versus Dapagliflozin In Type Ii Diabetic Male Rats
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Abstract
Background: type 2 diabetes mellitus (DM) is the most prevalent type of
DM and it is mainly related to inadequate response to insulin (reduced
insulin sensitivity) and insulin resistance in peripheral tissues.
Cardiovascular complications related to diabetes are major contributors in
the morbidity and mortality of diabetic population. Among diabetesrelated
cardiovascular complications, is diabetic cardiomyopathy (DCM)
that refers to myocardial left ventricular dysfunction in absence of
obvious coronary artery disease and atherosclerosis.
There is a clear link between renin-angiotensin system hyperactivity and
diabetes-induced myocardial injury. Therefore, angiotensin II receptor
blockers have a possible protective role in DCM.
Sodium–glucose cotransporter type 2 (SGLT2) inhibitors had approval to
be used as anti-diabetic medications in the last decade. Independent of
their anti-hyperglycemic effects, SGLT2 inhibitors have been shown in
several experimental studies to have positive cardiovascular benefits.
The present study was conducted to compare the cardioprotective effects
of valsartan, an angiotensin II receptor blocker, and dapagliflozin (Dapa),
SGLT2 inhibitor, and the possible underlying mechanisms, as well as the
combined effect of both drugs against DCM in type 2 diabetic rats.
Methods: 50 male albino rats were divided randomly into 5 groups (10
rats /group): control, diabetic group, valsartan treated group, Dapa treated
group, valsartan and Dapa treated group. By the end of the study (9
weeks), rats were weighed and echocardiography was done. Also, serum
fasting glucose, serum fasting insulin, HOMA-IR, serum IL6, IL8,
myocardial GSH & MDA content and cardiac relative gene expression of
MMP2, MEF2 and Bax/Bcl2 ratio were measured. In addition, cardiac
histopathology (using Hematoxylin & Eosin and Masson trichrome
stains), immunohistochemical stain of coronary microvasculature (CD31
immunoexpression) and morphometric studies for percentages of
collagen fibers area and area of CD31immunoexpression were assessed.
Results: diabetic group exhibited significant decline in systolic function,
significant myocardial damage and fibrosis, significant weight loss,
significant elevation in blood glucose, insulin, HOMA-IR, serum IL6,
IL8, myocardial MDA and Bax/Bcl2 ratio. Also, diabetic rats showed
significant decline in myocardial GSH and % area of
CD31immunoexpression. Treatment of diabetic rats with valsartan or
Dapa or combined therapy caused significant improvement of all assessed
parameters.
Conclusion: treatment of type 2 diabetic rats with valsartan or Dapa
exhibited cardioprotective effects against DCM. There was no advance of
administration of one drug above the other. But, higher cardioprotective
effect was obtained with combined administration of both drugs.