Effect of Selenium on Carbimazole Induced Alterations in Testicular Function in Albino Rats Abeer A. Shoman MD, Noha I. Hussien MD, Nessrine I. Ahmad MD* and Hanan T. Emam MD** Departments of Physiology, Histology* and Pharmacology** Faculty of Medicine, Benha University, Egypt. Abstract Carbimazole is an antithyroid drug used in treatment of hyperthyroidism. The use of Carbimazole was associated with various adverse effects in male reproductive system. Spermatogenesis is an extremely active process with high rate of cell division that leads to high rates of mitochondrial oxygen consumption by the germinal epithelium. However, oxygen tensions in this tissue are low so both spermatogenesis and Leydig cell steroidogenesis are vulnerable to oxidative stress. Testes and epididymes contain high concentrations of Selenium indicating its vital role during spermatogenesis to improve semen quality. This study was designed to evaluate the effect of Carbimazole on testicular activity in albino rats and the ameliorative role of selenium. The rats in this study were divided into 4 groups. Group (1) that were served as normal control, Group (2) were orally given Carbimazole Group (3) were orally given sodium selenite and Group (4) that were orally administered Carbimazole and sodium selenite for 8 weeks. Testicular reduced glutathione concentration (GSH), Testicular malondialdehyde (MDA) concentrations, Epididymal sperm count, Sperm motility, Sperm abnormalities, serum testosterone, LH, FSH levels and testicular histopathology were examined. From this study we can conclude that, treating animals with selenium causes improvement in normal testicular function of rats. Also we concluded that combination of selenium with Carbimazole showed improvement in testicular alterations induced by Carbimazole in rats. 1
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Effect of Selenium on Carbimazole Induced Alterations in Testicular
Function in Albino RatsAbeer A. Shoman MD, Noha I. Hussien MD, Nessrine I. Ahmad MD* and
Hanan T. Emam MD**
Departments of Physiology, Histology* and Pharmacology**
Faculty of Medicine, Benha University, Egypt.
Abstract Carbimazole is an antithyroid drug used in treatment of hyperthyroidism. The use of Carbimazole was associated with various adverse effects in male reproductive system. Spermatogenesis is an extremely active process with high rate of cell division that leads to high rates of mitochondrial oxygen consumption by the germinal epithelium. However, oxygen tensions in this tissue are low so both spermatogenesis and Leydig cell steroidogenesis are vulnerable to oxidative stress. Testes and epididymes contain high concentrations of Selenium indicating its vital role
during spermatogenesis to improve semen quality. This study was designed to evaluate the effect of Carbimazole on testicular activity in albino rats and the ameliorative role of selenium.
The rats in this study were divided into 4 groups. Group (1) that were served as normal control, Group (2) were orally given Carbimazole Group (3) were orally given sodium selenite and Group (4) that were orally administered Carbimazole and sodium selenite for 8 weeks. Testicular reduced glutathione concentration (GSH), Testicular malondialdehyde (MDA) concentrations, Epididymal sperm count, Sperm motility, Sperm abnormalities, serum testosterone, LH, FSH levels and testicular histopathology were examined. From this study we can conclude that, treating animals
with selenium causes improvement in normal testicular function of rats. Also we
concluded that combination of selenium with Carbimazole showed improvement in testicular alterations induced by Carbimazole in rats.
1
Introduction
Carbimazole is an antithyroid agent that decreases the uptake and
concentration of inorganic iodine by thyroid; it also reduces the formation
of diiodotyrosine and thyroxin (1). Serum Carbimazole is a common oral
treatment for hyperthyroidism. On the other hand, the use of Carbimazole
was associated with various adverse effects (2). Carbimazole produced
mild necrosis of renal tubules in rats. Carbimazole was capable of
inducing acute pancreatitis, pulmonary hemorrhage and necrotizing
glomerulonephritis and cholestatic hepatitis in 33-year old female (3).
Reactive oxygen species (ROS) are molecules that have at least one
unpaired electron, rendering them highly unstable and highly reactive in
the presence of lipids, amino acids and nucleic acids. At physiologic
levels, ROS are essential for normal reproductive function, acting as
metabolic intermediates in the metabolism of prostanoid, in the regulation
of vascular tone, in gene regulation, and in facilitated sperm capacitation
and acrosome reaction(4). However, at higher concentrations, they exert
negative effects. The main source of ROS production in seminal plasma
is leukocytes and immature spermatozoa. Spermatids and mature
spermatozoa are deemed highly sensitive to ROS because their
membranes are particularly rich in polyunsaturated lipids. By altering
membrane integrity, ROS may impair sperm motility and morphology
and can lead to sperm cell death (5).
Spermatogenesis is an extremely active replicative process capable
of generating approximately 1,000 sperm a second. The high rates of cell
division inherent in this process lead to high rates of mitochondrial
oxygen consumption by the germinal epithelium. However, the poor
vascularization of the testes means that oxygen tensions in this tissue are
2
low and that competition for this vital element within the testes is
extremely intense (6).
The testes contain an elaborate array of antioxidant enzymes and
free radical scavengers to ensure that the twin spermatogenic and
steroidogenic functions of this organ are not impacted by oxidative stress.
These antioxidant defense systems are of major importance because
peroxidative damage is currently regarded as the single most important
cause of impaired testicular function (7).
Selenium (Se) is an essential element for normal testicular
development, spermatogenesis, and spermatozoa motility and function.
Se may protect against oxidative DNA damage in human sperm cells.
However, the exact mechanism by which Se eliminates oxidative stress to
improve male fertility and semen quality in humans is still controversial (8). There are at least 25 selenoproteins in the human body, and they help
maintain sperm structure integrity (9).
The best-characterized spermatozoal effects of Se deficiency are:
important loss of motility, breakage at the midpiece level and increased
incidence of sperm-shape abnormalities, mostly of the sperm head. This
is evidenced by studies that reported a significant correlation between Se
levels in seminal plasma and the percentage of morphologically normal
sperm in a sample (10).
Selenium is an essential element important in many biochemical
and physiological processes including the biosynthesis of coenzyme Q (a
component of mitochondrial electron transport systems), regulation of ion
fluxes across membranes, maintenance of the integrity of keratins,
stimulation of antibody synthesis, and activation of glutathione
peroxidase (11). Selenium ameliorated the testicular damage and oxidative
stress induced by Carbimazole in albino rats (12).
3
The present work aims to investigate the effect of selenium on
histology of testis, serum testosterone level, LH, FSH, Testicular GSH,
Testicular MDA and semen analysis alterations induced by Carbimazole
in male albino rats.
MATERIALS AND METHODSAnimals
Thirty two male adult albino rats of locally breaded strain
weighing between 150+ 5 g at the beginning of the study were used. They
have acclimatized for one week in groups (8/cage) in fully ventilated
room at ordinary room temperature. Rats were allowed to water and
balanced diet.
At the beginning of the experiment they were divided into 4 groups
each contained 8 rats:
Group I: Control normal rats. They received no drugs
Group II: Animals of this group were orally given Carbimazole (1.35
mg/Kg b.w) dissolved in water, daily for 8 weeks (13).
Group III: animals of this group were orally given sodium selenite (10
μg/Kg b.w) dissolved in water, daily for 8 weeks (14).
Group 4: animals of this group were orally administered Carbimazole
(1.35mg/Kg b.w) and sodium selenite (10μg/Kg b.w) for 8 weeks. The
treated animals were sacrificed by cervical decapitation after 8 weeks of
treatment.
Drugs:
Selenium (sodium selenite): gray powder 5gm in bottle from
(Sigma chemicals Co., U.S.A.).
Carbimazole: 10 mg Tablet (Ambica Intl Trading).
Hematoxylin and eosin: (E. Merk, Darmastadt.,) [U.S.A.].
*** Significant P < 0.001 compared with control normal rats.
10
Table (5): Effects of combination of selenium and Carbimazole on serum levels of testosterone, LH &FSH, testicular GSH and testicular MDA in male rats. (Mean± SD) (n = 8).
*** Significant P < 0.001 compared with Carbimazole treated rats.
Table (6): Effect of combination of Carbimazole and selenium on sperm count, sperm motility and sperm abnormalities in male albino rats
parameters Group
Sperm count(10)6
Sperm motility%
Sperm abnormalities%
Carbimazole group 11.45±0.12734.474±0.24824.165±0.191
Group received carbimazole and
Selenium
14.541±0.327***51.614±0.430***11.919±0.293***
*** Significant P < 0.001 compared with Carbimazole treated rats.
Fig (1-a) Fig (1-b)
.uoc mreps tom mreps .ba mreps0
01
02
03
04
05
06
#
#
#
.zamibrac neles&.brac
tset HL HSF HSG ADM0
2
4
6
8
01
21
## #
##
zamibraC .niles&.bac
# Significant (P < 0.001) compared with Carbimazole treated rats.
Fig. (1-a) & Fig. (1-b) Effects of combination of selenium and Carbimazole on serum levels of testosterone, LH &FSH, testicular GSH, testicular MDA, sperm count, sperm motility and sperm abnormalities in male albino rats
11
Fig. (2): Cut section of testicular tissues of control normal rats showing no remarkable
pathologic changes (H&E100)
Fig. (3): Cut section of testicular tissues of rats received Carbimazole (H&E100)
12
Fig. (4): Cut section of testicular tissues of rats received selenium (H&E100)
Fig. (5): Cut section of testicular tissue of rats received both carbimazole and selenium
(H&E100)
Fig. (6): detached head Fig. (7): double head and bifid tail
R. P. and Ray, B. R. (2008): Protective effect of sodium selenite
22
and zinc sulfate on intensive swimming-induced testicular
gamatogenic and steroidogenic disorders in mature male rats.
Appl. Physiol. Nutr. Metab., 33(5), 903-914.
31- Kashanian, S.; Gholivand, M. B.; Ahmadi, F. and Ravan, H.
(2008): Interaction of diazinon with DNA and the protective role
of selenium in DNA damage. DNA Cell Biol., 27(6), 325-532.
32- Grotto, D.; Barcelos, G. R.; Valentini, J.; Antunes, L. M.; Angeli,
J.P.; Garcia, S. C. and Barbosa, F. Jr. (2009): Low levels of
methylmercury induce DNA damage in rats: protective effects of
selenium. Arch. Toxicol., 83(3), 249-254.
33- Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z,
Ghozzi H and Hammami S, (2003): Sperm oxidative stress and
the effect of an oral vitamin E and selenium supplement on semen
quality in infertile men. Arch Androl ;49:83-94.
34- ashock AG. And Lucky H.(2011): Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified? Indian jurnal of urology; 27(1), 74-85.