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Advances in Environmental Biology, 7(14) December 2013, Pages: 4768-4772
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Advances in Environmental Biology
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Investigating Effect of Raloxifene on the Factors of Blood Urea Nitrogen, Uric Acid and
Creatinine in Female Rats
1,2
6
Ebadi Zahra, 1,3Kargar Jahromi Hossein, 4Ghorishi Fakhrossadat, 4Zahedi Ali, 5Khodaparast Zahra,
Azhdari Sara, 6Farzam Mohammad
1
Jahrom University of Medical Sciences, Jahrom, Iran.
Developmental Biology, Islamic Azad University, Jahrom, Fars, Iran.
Young Researchers Club Elite, Jahrom Branch, Islamic Azad University, Jahrom, Iran.
4
The Departmant General of Bandar Abbas Province Education.
5
Department of Biology, Islamic Azad University, Arsanjan, Fars, Iran.
6
Department of Anatomy and Embryology, International Branch, Shiraz University, Shiraz, Iran.
2
3
ARTICLE INFO
Article history:
Received 15 November
Received in revised form 14
January 2014
Accepted 20 January 2014
Available online 20 February 2014
Key words:
Raloxifene Blood urea nitrogen
Uric acid Creatinine, Rat.
ABSTRACT
Introduction: Raloxifene is from SERM drugs groups (selective estrogen receptor
modulators). These drugs in some tissues have similar effects of estrogen (agonist) and
prevent the effects of estrogen in other tissues (antagonistic). In this study, the effects of
raloxifene on the factors of blood urea nitrogen, uric acid and creatinine in rats were
measured. Methods: 40 female Wistar rats were divided randomly into 5 groups. The
first group (control group) did not receive any medication. The second group (sham
group) only distilled water injected. Experimental group 1 received raloxifene 5 mg/kg
daily, experimental group 2 received raloxifene 10 mg/kg, and experimental group 3
received raloxifene 20 mg/kg that all was based on body weight and were received
intraperitoneally. At the end of 30 days, the rats were bled and concentration of blood
serum of urea nitrogen, uric acid and creatinine were measured. Data were analyzed
using SPSS software version 18. Results: The results show that the concentration of
creatinine in experimental groups 1, 2 and 3 showed a significant increase compared to
the control group. Concentrations of Blood urea nitrogen and uric acid have no
significant change compared to control group. Conclusion: We may conclude that
raloxifene in low rates, causes changes in concentration of Renal factors.
© 2013 AENSI Publisher All rights reserved.
To Cite This Article: Ebadi Zahra, Kargar Jahromi Hossein, Ghorishi Fakhrossadat, Zahedi Ali, Khodaparast Zahra, Azhdari Sara, Farzam
Mohammad., Investigating effect of raloxifene on the factors of blood urea nitrogen, uric acid and creatinine in female rats. Adv. Environ.
Biol., 7(14), 4768-4772, 2013
INTRODUCTION
Brand name of Raloxifene drug is EVISTA [1]. Because this drug, only is effective on sex hormone of
females, it is prescribed only for women. Raloxifene is as tablet and consumes one tablet per day and it is taken
orally [2]. This medication is used to treat osteoporosis [3]. Raloxifene is as estrogen receptor of selective
nonsteroidal regulator and it has recently been set up to help improve common diseases in postmenopausal
women. Raloxifene is to be from SERM drug groups (selective estrogen receptor modulators). These drugs in
some tissues have similar effects of estrogen (agonist) and prevent the effects of estrogen in other tissues
(antagonistic) [4 and 5]. Raloxifene is prescribed for the treatment of hormone-responsive cancers and in this
tissue as an antagonist, prevents the activation of estrogen receptor of androgen. Estrogenic and anti-estrogenic
effects of raloxifene are entirely clear on the organization and regulation of the nervous system in controlling
reproductive function. Since 2007, stated that raloxifene is useful for reducing the risk of breast cancer in
postmenopausal women who are facing breast cancer. Raloxifene hydrochloride, a pale yellow solid which is
slightly soluble in water [4,5]. In fact, we can say that raloxifene has an estrogen replacement therapy for those
who are at risk for osteoporosis [6]. Raloxifene, reduces bone resorption, and on target tissues act as an
antagonist [7]. Raloxifene metabolizes by the liver, but in the people with nufruity syndrome who are at high
risk for blood clots in the veins of the heart, it is better not to use Raloxifene [9,8]. On the other hand, the effect
of raloxifene as modulators of the selective estrogen receptor, has been investigated to prevent functional and
histological changes in the kidneys of rats with type 2 diabetes. The results of this study suggest that raloxifene
significantly, reduces Mzanzhyal cell proliferation and fibronectin accumulation in the kidneys of diabetic rats
Corresponding Author: Ebadi Zahra, Islamic Azad University of Jahrom Branch, Jahrom, Iran.
Tel: +989372777533; E-mail: ebadizahra96@ yahoo.com
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Advances in Environmental Biology, 7(14) December 2013, Pages: 4768-4772
[10,11]. Also, it is reported that Raloxifene reduces Collagen synthesis of renal Mzanzhyal cell and noting that
the raloxifene for treatment of kidney diseases can be useful [12]. The present study examined the effect of
raloxifene drug on renal parameters changes.
Method:
All work ethic with laboratory animals has been complied. 40 adult female Wistar rats, weighing 200 ± 5%
grand age of 100 - 110 days were obtained from the Jerome research center. Rats were placed in the animals
house of Jahrom Islamic Azad university for 21 days in laboratory conditions include temperature of 21 ± 2 ° C ,
12 hours light and 12 hours dark. Rats were used standard foods (pellet). Also, water from special glass bottles
were given to them. Cages were disinfected with 70% alcohol 3 times a week. The lethal dose of the drug was
40 mg. Accordingly, doses of minimum, average and maximum were determined. In this case, maximum dose
was half of Lethal dose, average dose was half of maximum dose, and minimum dose was half of average dose.
Raloxifene drug is soluble in water. In this study, distilled water was used as solvent. All solutions were
prepared fresh each morning . The rats were divided into 5 groups of 8 as follows :
Control group (A) : They did not receive any medical, and nutrition, and all conditions were similar to other
groups.
Sham group (B) : Based on body weight of rats, they received distilled water.
Experimental group 1 (C1) : Amount of drug was based on their weight, they received 30 mg raloxifene
tablet dissolved in 1 ml of distilled water.
Experimental group 2 (C2) : Amount of drug was based on their weight, they received 60 mg raloxifene
tablet dissolved in 1 ml of distilled water.
Experimental group 3 (C3) : Amount of drug was based on their weight, they received 120 mg raloxifene
tablet dissolved in 1 ml of distilled water.
After the end of the 21 day period, rats of all groups after weighing were anesthetized with ether, and blood
samples were collected from their heart by 5 cc syringe, and after separation blood serum, concentration of
factors of blood urea nitrogen (BUN), uric acid (UA), and creatinine (Cr) in the laboratory of Jahrom medical
university were measured. For comparison between treatments One-way ANOVA followed by t-test and
Duncan test was used that was for multiple comparisons between groups. Significance level (P<0/05) was used.
Data analysis and statistical testing were performed using SPSS software, version 18.
Results:
The results showed that concentration of blood urea nitrogen in the groups receiving raloxifene drug, did
not show significant change compared to control group (table 1).
Table 1: Changes about blood urea nitrogen in different groups
The results show that changes in uric acid in experimental groups have no significant changes compared to
control groups.
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Advances in Environmental Biology, 7(14) December 2013, Pages: 4768-4772
Table 2: Changes about blood urea nitrogen in different groups
Concentration of creatinine in experimental groups 1, 2 and 3 have no significant increase compared to
control group.
Table 3: Changes about blood urea nitrogen in different groups
Discussions:
The urinary system is one of the major body systems that are more routine protocols for testing to determine
the amount of toxicity. The kidneys play a major role in filtration, metabolism and excretion of xenobiotics or
metabolic products. Chemicals or other active metabolic forms may transfer from plasma to renal tubules and to
multiply the concentration level that can be found in other tissues. In addition, the kidneys receive
approximately 25% of cardiac output that it increases the distribution of chemicals to the kidneys and
Measurement of blood urea nitrogen and creatinine are valid tests for kidney functions [13]. In researching
conducted in the past stated that the symptoms of kidney failure and damage to the tubules of the kidney can be
as follows : 1. Increase of creatinine clearance, increase of BUN and uric acid serum. 2. Increase of tissue
damage in pathology studies and other cases can be cited [14]. In the present study the changes in blood urea
nitrogen and uric acid is not statistically significant But what is certain is that the groups that had received a
higher dose of the drug, increase in blood urea nitrogen and uric acid concentration is observed which can not be
ignored. Studies indicate that raloxifene causes morphometric changes in the kidney [15]. Studies show that
Raloxifene acts as Selective Estrogen Receptor. In fact function of alpha and beta receptors of estrogen
influence on kidney cells. And by this way, causing an increase in cell sizes [16,17]. Some studies suggest that
raloxifene, binds to alpha and beta receptors of estrogen. Alpha receptor is in Glomerular and near and far
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complex tubular [16,17]. Estrogen increase, reduces calcium absorption in near and far complex tubular, so, the
transfer or absorption of sodium increases. Estrogen also, transfer of sodium chloride and activation of sodium
potassium ATP pump, increase in near and far complex tubular that this lead to enlargement of near and far
complex tubular cells. Since raloxifene acts as an estrogen, this lead to enlargement of kidney cells [16, 17]. In
the present study this effect occurs as changes in the concentrations of blood urea nitrogen and creatinine and
uric acid and What is certain is that increase of these factors in blood serum indicate damage to kidney tissue. In
the present study, changes about uric acid and blood urea nitrogen is not significant But creatinine in a dose
dependent manner, has a significant increase compared to control group that indicate damage to kidney tissue.
Probably the causes that factors of blood urea nitrogen and uric acid have not significant changes is due to dose
and time duration of drug and type of laboratory animal. Previously expressed that Raloxifene by inhibiting AP1 activity prevents stimulation of TGF-B1 and expression of fibronectin. In fact, raloxifene inhibits fibronectin
expression through AP-1 mechanism that prevents the proliferation of Mzanzhyal cells [18]. It may be that this
effects occur as changes in renal tissue and so change in secretions of factors in blood urea nitrogen, creatinine,
uric acid.
Conclusion:
The results show that with doses used in the study, changes in blood urea nitrogen and uric acid is not
significant, but changes related to creatinine are significant that indicate negative effect of drug. Probably, drug
with effect on alpha and beta receptors and change in kidney tissue causes changes of kidney morphometric and
changes in secretion of kidney factors. It is recommended that, in future, the effects of high doses of raloxifene
on all changes of kidney factors be examined.
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