PTU Induction Provide Quick Screening of Hypo and Hyperlipidemia
Idress Hamad Attitalla
Lipids are the small hydrophobic molecules; found in every kind of living organisms
and can be categorized as fatty acyls, glycerolipids, glycerophospholipids,
gphingolipids, steroids, prenol lipids, saccharolipids and polyketides (Fahy
et al., 2009). They are the important source of energy and are the
part of various cellular membranes. Any disturbance in bodys lipid profile,
especially production of oxidized lipids can cause disease and disturb the platelet
related immune system (Podrez et al., 2007).
As higher level of lipids, called hyperlipidemia, can increases the risk factors
of diseases e.g., myocardial infarction and ischemic heart disease (Nordestgaard
et al., 2007). It can also cause mortality; in Denmark from 1976-2004,
7818 peoples died due to increased levels of non-fasting cholesterol. Moreover,
due to these higher cholesterol levels 1793 become myocardial infarction and
3479 peoples become ischemic heart disease patients. To lower the hyperlipidemia
high dosed statin therapy is frequently used, but it can cause muscle disease
and limits the activities of patient (Bruckert et al.,
2005). Its muscle disease onset time due to high dosage was one month in
832 (10.5% of total studied patients) hyperlipidemia patients, thus there is
need of more reliable drugs. The efficiency or possible side effects of drugs
can be valuably recognized through in vivo studies (Doijad
et al., 2008). But human in vivo drug studies are tough and
sometimes failed to properly estimate the drug efficiencies because of individuals
varying metabolic characteristics (Rostami-Hodjegan and
Tucker, 2007). Thats why in vivo studies, before human trials
are performed in small animals (rats). But drug production is often limited
by the huge time requirements of animal in vivo trials. Because the hyperlipidemic
affects producing techniques in rats takes too long time, 2 weeks to 2 months
(Bashandy, 2007; Zhu et al.,
2008). Consequently it delays the drug manufacturing and availability in
market; therefore there should be a way to produce the required disease effects
quickly in experimental models. This may positively regulate the drug investigation
in laboratory trials.
Propylthiouracil (PTU) is well known for its hypothyroidism effects and used
as drug to maintain the thyroid hormone production for more than 50 years (Cooper
and Rivkees, 2009). It can increase the body lipids when used in combination
with bile salts, thus in certain situations it can enhance the lipid levels
(Zhang et al., 2007). Recently Hasimun
et al. (2011) recommended PTU as an efficient hyperlipidemic agent
to fasten the estimation of drugs efficiency. They orally administrated
the rats with 10 mg kg-1 b.wt. PTU daily for seven days and add 0.01%
PTU in rats drinking water. They compared these animals with non-PTU adminsitrated
and orally induced PTU rat groups. All these rat groups were fed with high cholesterol
food 1 h before the examination. A significant difference in these animals was
observed, which was due to increased levels of total serum cholesterol. Highest
elevation of cholesterol levels occurred in PTU treated animals (Oral + PTU
water induction). Its hyperlipidemic property was observable through the increased
levels of cholesterol in serum and liver, while its induction caused a decrease
in cholesterol secretion through feces. Moreover, a high dose of cholesterol
(400 mg kg-1 b.wt.) without PTU induction was ineffective in producing
hyperlipidemia even after 6 hours of its application. Thus PTU was efficient
in rapidly producing hyperlipidemia and showed a significant increase in cholesterol
levels after the 2 h of induction. These PTU hyperlipidemic effects were helpful
in quick examining of hypolipidemic drugs. As the application of simvastatin
and ezetimibe (hypolipidemic drugs) in different PTU hyperlipidemic animals
reduced the increased levels of serum cholesterol and maintained them below
100 mg dL-1. Furthermore, these drugs caused a significant reduction
in liver cholesterol and increased its secretion through feces, which was observable
within 2 h of assessment. According to PTU technique most appreciable hypolipidemic
activity was of simvastatin (5 mg kg-1 b.wt.), it significantly decreased
the liver cholesterol and increased its excretion. On the other hand ezetimibe
application was more effective in lowering the serum cholesterol levels. Thus
PTU oral and watering application provided excellent results for rapid examination
of hypolipidemic and hyperlipidemic effects. As cholesterol food caused hyperlipidemia,
was observable shortly after 2 h of its application in PTU treated animals.
Whereas its application in non-PTU treated animals required long time to induce
hyperlipidemic. Likewise the hypolipidemic effects of any substitution were
also observable in PTU treated animals, which can be determined within 2 h,
after drug application.
Hyperlipidemia is a condition of increased cholesterol (lipid) levels in body,
which leads towards heart diseases and its related complications. It can be
treated through hypolipidemic drugs, but large time requirements of laboratory
experiments hindered their rapid production. As the preparations of specific
metabolic diseased condition in animals is time consuming procedure. According
to Hasimun et al. (2011) conducted research PTU
application in rats diet and water could reduce these time expenditures.
As PTU application made these animals hyperlipidemic shortly after the application
of cholesterol food. It helped in the rapid examination of drugs and estimated
the drug efficiency within 2 h. Thus PTU provides a novel approach by constraining
the time requirements of hyperlipidemic experimental models and hastens the
drug inspection. Its use in experimental trials will helps to positively accelerate
the investigation of drugs hypolipidemic property.
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