الفهرس 
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Abstract
Summary: and Conclusios Metabolic syndrome (MS) is a constellation of abnormalities.
The major components of the metabolic syndrome are obesity,
glucose intolerance, insulin resistance, low levels of HDL-C,
elevated LDL-C and TGs levels, and elevated BP. Hypertension is
the key component of the metabolic syndrome. Therefore the aim
of treatment of hypertension in a patient is not only to control high
BP but also to reduce the associated CV risk factors and treat
other co-morbidities.
Despite the cumulative evidence on the cardioprotective
effects of β-blockers, their use in diabetic patients has been
controversial and is still low.
Carvedilol, a third-generation β-blocker with antioxidant
properties, has a unique pharmacological profile and promising
effects on metabolic parameters. So, the aim of our research was
to study the effects of carvedilol treatment on some metabolic
parameters in different co-morbidities such as diabetes or
hyperlipidemia.
The present study was designed to investigate the effects of
carvedilol on the levels of glucose, total cholesterol (TC),
triglycerides (TGs), high density lipoprotein-cholesterol (HDL-C)
and low density lipoprotein-cholesterol (LDL-C) in three
experimental models of normal, type-1 diabetes mellitus and
hyperlipidemia.
Animals used were male albino rats weighing 250-300 g.
Groups of rats were control and treated normal, diabetic and
hyperlipidemic, 12 rats each.
Experimental type 1 diabetes mellitus was induced in rats by
injecting them with alloxan monohydrate in a dose of 100 mg/kg
body weight intraperitonealy. Two days later, BGL of rats was
measured and rats with BGL above 250 mg/dl were considered
diabetic and selected.
The surface active agent triton WR 1339 was used for
induction of experimental hyperlipidemia. Rats were starved for 18
hours, and then injected with 0.5 ml of the 10% solution of triton
WR 1339 intraperitonealy. Triton injection causes a sharp increase
in serum lipids in the first 24 hours from injection (phase 1) during
which the experiment was performed, and then retunes nearly to
normal levels in the second 24 hours (phase 2).
A 10% solution of the surfactant tween 80 was used for
dissolving of carvedilol doses.
Animals were assigned to receive 0.5 ml of the solvent alone
or the solvent containing 10 mg/kg body weight of the drug by
intraperitoneal injection as follows:
1- Group I: Normal control rats receiving the solvent solution.
2- Group II: Normal rats receiving carvedilol.
3- Group III: Diabetic control rats receiving the solvent solution.
4- Group IV: Diabetic rats receiving carvedilol.
5- Group V: Hyperlipidemic control rats receiving the solvent
solution.
6- Group VI: Hyperlipidemic rats receiving carvedilol.
from each group, blood samples were taken at zero time
(before injection) to determine the baseline levels and then at 15,
30, 60, 120, 180 and 240 minutes from injection in order to
determine the serum levels of glucose, total cholesterol,
triglycerides and high density lipoprotein-cholesterol.
The acute toxicity of carvedilol in rats was evaluated in the
three experimental models; normal, diabetic and hyperlipidemic
rats. 13 rats were used for the determination of the LD50 of
carvedilol in the three models. In each group, there were two sets
of experiments. Rats of the first set received graded doses
carvedilol to determine the approximate range of toxicity and
according to the number of animals died, doses of the second set
were selected. At the end of the experiment, the LD50 of carvedilol
was calculated.
The results of the present study revealed that:
Alloxan-monohydrate when intraperitonealy injected in a dose
of 100 mg/kg body weight in rats lead to a sharp elevation in BGL
after 2 days from injection.
The 10% solution of the surface active agent triton WR 1339,
when injected intraperitonealy in a dose of 0.5 ml/rat lead to
elevation of serum lipids especially total cholesterol and
triglycerides (induced hyperlipidemia) after 24 hours from injection.
The intraperitoneal injections of carvedilol in a dose of 10
mg/kg body weight in rats lead to the following effects on the
tested metabolic parameters:
a) Elevation of BGL significantly in the three tested groups.
b) In non-diabetic non-hyperlipidemic rats group, carvedilol
treatment elevated TC and LDL-C level while lowered both
TGs and HDL-C levels.
c) In diabetic rats group, carvedilol lowered measured lipid
parameters (TC, TGs, HDL-C and LDL-C).
d) In the hyperlipidemic rats, carvedilol treatment increased TC,
TGs and HDL-C levels while decreased LDL-C levels.
Testing the toxicity of carvedilol was dependent on evaluating
its median lethal dose (LD50) in the three experimental models and
the results revealed that:
a) In normal rats, the LD50 of carvedilol was 471.2 mg/kg.
b) In diabetic rats, the LD50 of carvedilol was 141.4 mg/kg.
c) In hyperlipidemic rats, the LD50 of carvedilol was 288.5 mg/kg.
This reveals that the toxicity of carvedilol increases with
disease states where the drug was least toxic in NDNH rats, more
toxic in hyperlipidemic rats and most toxic in diabetic rats.
Finally, all patients with diabetes mellitus or hyperlipidemia
receiving carvedilol therapy should subject
monitoring of glucose tolerance and lipid metabolism which will
reveal any adverse effect that might occur during treatment with
carvedilol.
Metabolic syndrome is a constellation of abnormalities
including obesity, glucose intolerance, insulin resistance and
dyslipidemia in which hypertension is considered the key
component.
Diabetes mellitus is a disease of major metabolic
derangements and abundant health hazards.
The selection of drugs for cardiovascular complications in
patients possessing one or more of the metabolic syndrome
components such as diabetes mellitus or hyperlipidemia should be
based on well known benefits and associated risks.