Effects of Sodium Selenite on the Ultrastructure of the Kidney...

Journal of Applied Sciences Research, 3(9): 803-810, 2007
© 2007, INSInet Publication
Effects of Sodium Selenite on the Ultrastructure of the Kidney Cortex in Normal Rats
Fairoze Khattab I. Khattab
Department of Zoology , Faculty of Science, Ain Shams Universty Cairo, Egypt
Abstract: This study aims to reveal the histological and ultrastructural effects of sodium selenite on the
kidney cortex of normal rats. The over supply of selenium in diet are associated with the occurrence of
clinical symptoms to humans and animals. Rats used in this study were divided into five groups, one as
a control and the other four groups were treated with sodium selenite at doses of 1 and 2 mg/kg body
weight for 5 and 10 days. The histopathologic investigation revealed renal cells damage after 5 days of
treatment with lower doses of sodium selenite followed by necrosis in the kidney from rats with higher
doses at 10 days. Ultrastructural lesions similar to the light microscopic lesions were most common on
the proximal convoluted tubules, distal convoluted tubules and collecting tubules. After 5 days of treatment
with low doses, initial cellular changes included vacuolation of cells and mid to moderate degenerative
lesions were scattered through the kidney cortex with loss of cellular detail and hydropic degeneration and
formation of apical buds and cellular rupture, in distal convoluted tubules and collecting tubules observed
after 10 days of treatment with both low and high doses. The range of structural damage in proximal
convoluted tubules was more restricted than in distal convoluted tubules and collecting tubules cells.
Key words: sodium selenite- rats- kidney- histopathology- ultrastructure.
INTRODUCTION
studied before and also noticed swelling and
vacuolation of epithelial cells of proximal tubules and
in some mice, tubular necrosis was observed [3 ].
Organic selenium compounds (selenosemicarbazide)
are the form more easily assimilated, compared to
inorganic sodium selenite, which is confirmed by an
elevated content of selenium in the internal organ of
mice after organic and inorganic supplementation with
selenium have been reported on histopathologic and
ultrastructural changes [1 1 ,1 2 ,1 8 ].
The aim of the present study was to investigate
possible histological and ultrastructural changes in the
kidney cortex of rats treated with sodium selenite.
Selenium (Se) is an essential trace element, and its
clinical significant in various pathophysiologic
conditions has been increasingly recognized [2 ,8 ,1 6 ,1 7 ].
Selenium is an integral component at catalytic
sites of the enzyme glutathione peroxidase in
several tissues [1 9 ].
The principle role of selenium is associated with
the control of lipid peroxidation because this trace
element is a component of selenoenzymes contributing
to the antioxidant system [4 ,6 ,1 4 ,2 1 ].
Both deficiency and over supply of selenium in a
diet are associated with the occurrence of
clinical symptoms including Kashan and Kashin
Beck disease [2 2 ].
Experimental animal studies for selenium toxicity
have been reported.
Selenium has protective effects against mercury
toxicity in rat kidney [9 ] and Selenium also used to
diminish the toxic effects of the cadmium on the
antioxidant enzyme system, which in turn affects the
membranes structures such as mitochondria and
endoplasmic reticulum [7 ].
Selenium deficiency reduces glutathione peroxidase
activity have been reported in diet of glomular disease
and in diet of tubular epithelium in normal rats [1 ,1 0 ].
Acute tubular injury of mice kidney induced by
dimethyl selenide intratracheal instillation have been
M ATERIALS AND M ETHODS
Fifty adult male rats weigh 100-150 mg each were
used as experimental animals. Rats were assigned at
random to five groups of 10 rats each. One group of
rats were designated as control group and other four
groups were designated as experimental groups of rats
were administered orally by stomach tube two doses of
sodium selenite (1 mg and 2 mg/kg body weight).
Rats
of
control
groups were administered
distilled water.
At 5 and 10 days after treatment, the rats were
sacrificed and the kidneys were removed and washed
in phosphate buffer. The kidney cortex was cut into 1
mm thick for light and electric microscopic
Corresponding Author: Fairoze Khattab I. Khattab, Zoology Dept., Faculty of Science, Ain Shams Univ. Cairo, Egypt
803
J. Appl. Sci. Res., 3(9): 803-810, 2007
examination. Then fixed in 2% formaldehyde and 2.5
glutraldehyde in 0.02 M phosphate buffer and then
placed
in
fresh
cold fixative for 24 hrs. in
refrigerator .The tissue was rinsed in cold phosphate
buffer (pH 7.4) and post fixed in 2% aqueous osmium
tetroxide for 2 hrs. at 4 o c. The samples were rinsed in
cold phosphate buffer, dehydrated in ethanol series and
embedded in epoxy resin. Blocks were sectioned
and semithin (1 um) sections were stained in
0.5 % toludine blue in borax and examined under
light microscope.
Ultrathin sections were cut and stained with 2%
aqueous uranyl acetate for 20 mins. and lead citrate for
20 mins. for examination and photographed using Joel
1200 Ex-II electron microscope.
Control Group: Light microscopic examination of the
kidney of control rats had normal renal cortical
structure, which consist of glomerulus (tuft of blood
capillaries surrounded by epithelial capsule, namely
Bowman's capsule, proximal and distal convoluted
tubules and the collecting tubules (Fig. 1)
By using the electron microscope control rats
kidney cortex has normal cortical ultrastructural
appearances. The cortex constitutes the major portion
of the kidney. The proximal convoluted tubules
(PCT), distal convoluted tubules (DCT) and collecting
tubules (CT) which are common in control rat kidney
cortex. The proximal convoluted tubules have luminal
brush border (Fig.2), these cells had large central
nuclei.
Golgi
apparatus lies in a supranuclear
portions. These brush border is composed of long
closely packed microvilli, and these cells contained
abundant elongated mitochondria and some lysosomes
(Fig.2).
Distal convoluted tubules are shorter than the
proximal tubules and the cells have no brush border
and the distal convoluted cells have central or apical
nuclei. In the basal cytoplasm there is a complex
interdigitation of lateral cell processes, radially oriented
mitochondria (Fig.3).
The collecting tubules vary in size contain
mitochondria and the cytoplasm containing apical
vesicles and the plasma membrane of the basal surface
is infolded but not deeply. Free ribosomes are
prominent and the nucleus is centrally located (Fig.4).
Fig. 1: Photomicrograph of a semithin section of the
control rat kidney cortex, showing proximal
convoluted tubules (P), distal convoluted
tubules (D) and collecting tubular cells (C).
Toludine blue stain. X1200.
Fig. 2: P h o to electro n
m ic ro g ra p h
o f p r o x im a l
convoluted tubular cell of control rat kidney
cortex, showing the apical microvilli (arrow),
mitochondria (M), lysosmes (L) and nucleus
(N). X15000.
Fig. 3: Photoelectron micrograph of distal convoluted
tubular cell of control rat kidney cortex,
showing the basal enfolding membrane
( a r r o w ) , n u c le u s (N ) a nd e lo n g a te d
mitochondria (M). X12000.
Fig. 4: Photoelectron micrograph of collecting tubular
cells of control rat kidney cortex, showing the
nucleus (N ), m itochondria (M ), basal
membrane (arrow) and tubular lumen (L).
X10000.
RESULTS AND DISCUSSIONS
804
J. Appl. Sci. Res., 3(9): 803-810, 2007
Figs. 7, 8: P hotoelectron micrographs of proximal
convoluted tubules after 5 days of
treatment with sodium selenite (1 mg/kg
body weight), showing apical brush border
(head arrow), swollen mitochondria (M),
dilated rough endoplasmic reticulum
(arrow), apical sm all vesicles (V ),
lysosomes (L) and nucleus (N). X12000,
X12000, respectively.
Fig. 5: Photomicrograph of a semithin section kidney
cortex after 5 days of treatment with sodium
selenite (1 mg/kg body weight), showing
cloudy, swelling tubular cells and vacuolar
degeneration (head arrows). X1200.
Fig. 6: Photomicrograph of a semithin section kidney
cortex 10 days after treatment with sodium
selenite (2 mg/kg body weight), showing the
necrosis of the tubular cells (head arrows)
with darkly stained pyknotic nuclei (arrow).
X900.
subcellular changes. The most significant ultrastructural
changes occurred in the proximal and distal convoluted
tubules and also in collecting tubules of the kidney
cortex after 5 days of treating rats with sodium selenite
(1 and 2 mg/kg body weight). Most proximal tubules
show a variety of ultrastructural changes. Some cells
show swollen microvilli, whereas others have
morphologically unchanged microvilli and many
vesicles were seen in apical region of these cells.
Swollen mitochondria were condensed with
diffusely darkened matrices and undistinguishable
cristea. The rough endoplasmic reticulum was dilated
in some areas of the cytoplasm and also dilated Golgi
apparatus was noticed (Figs.7 & 8).
The range of structural change in distal convoluted
tubules and collecting tubules cells were less affected
than in proximal collecting tubules cells after lower
doses of sodium selenite. Some distal convoluted
tubular cells had cytoplasmic vacuoles and the
mitochondria had abnormalities
in
appearance
and were condensed. And the nuclear chromatin
was condensed (Fig.9).
In the collecting tubules cells, the apical portion is
slight swollen forming apical cytoplasmic buds,
protrude into the tubular lumen. The mitochondria
are condensed and the chromatin clumped in
nucleus (Fig.10).
Experimental Groups: Light and electron microscopic
examination revealed subcellular changes after 5 and
10 days of treatment with two doses of sodium selenite
(1 and 2 mg/kg. body weight).
After Five Days: Sodium selenite supplementation in
a lower dose (1 mg/kg. body weight), for five days,
caused a slight histopathological changes the cells
exhibited cloudy swelling and showed smudy
appearance in the renal tubular cells (proximal and
distal convoluted tubules, and collecting tubules) and
showed also, vacuolar degeneration that is obvious in
narrowing of cells lumina and slight alterations of their
nuclear appearance (Fig.5).
A higher dose (2 mg/kg body weight) of sodium
selenite, revealed progressive histopathological changes.
The epithelial cells lining the convoluted tubules
(proximal and distal convoluted tubules and collecting
tubules) were partially detached and showed necrotic
changes with damage of brush borders and with darkly
stained pyknotic nuclei (Fig.6).
Electron
microscopic
examination
revealed
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J. Appl. Sci. Res., 3(9): 803-810, 2007
Fig. 9: Photoelectron micrograph of distal convoluted
tubules after 5 days of treatment with sodium
selenite (1 mg/kg body weight), showing
condensed mitochondria (M), nucleus (N) and
cytoplasmic vacuoles (V). X12000.
Fig. 10: Photoelectron micrograph of collecting tubular
cells after 5 days of treatment with sodium
selenite (1 mg/kg body weight), showing
apical cytoplasmic buds (head arrow), protrude
into the tubular lumen (L), mitochondria (M )
and nucleus condensed with chromatin (N).
X12000.
Fig. 11: P h o to e le c tro n
m ic ro g ra p h
o f p ro xim a l
convoluted tubules after 5 days of treatment
with sodium selenite (2 mg/kg body weight),
showing damaged mitochondria (M), nucleus
with clumped chromatin (N), cytoplasmic
vacuoles (V) and swollen apical microvilli
(head arrow). X12000.
Fig. 12: Photoelectron micrograph of distal convoluted
tubules after 5 days of treatment with sodium
selenite (2 mg/kg body weight), showing basal
folded membrane (arrow), irregular nuclei (N),
d e n s e m ito c h o n d r ia (M ) a n d a p i c a l
cytoplasmic buds (head arrow). X12000.
A higher dose (2 mg/kg body weight) of sodium
selenite, caused more restricted in structural change. In
renal tubular epithelium, the proximal convoluted
tubular cells showed more damage than those of low
doses. The apex of the proximal convoluted tubular
cells are swollen and extent into the lumen and also
observed vacuolization of the cytoplasm. The
condensed mitochondria are irregular in shape and
structure. The nucleus chromatin was also clumped at
nuclear membrane (Fig.11). Distal convoluted tubule
cells showed more damage in the cytoplasm, the basal
membrane is folded and the dense irregular elongated
mitochondria are noticed. On the other hand, the
nuclei of the lining cells of these tubules had obviously
migrated to the apices of these cells displaying an
irregular appearance (Fig. 12).
Collecting tubular cells had severe damage in some
cells by forming apical buds or by shrinkage and
decreased in length. The nuclei marked clumping of
their chromatin, the basal cell membrane are
Fig. 13: Photoelectron micrograph of collecting tubular
cells and a part of distal convoluted tubular
cells after 5 days of treatment with sodium
selenite (2 mg/kg body weight), showing the
apical cytoplasmic buds (head arrow), nucleus
(N), basal folded membrane (arrow) and
damage mitochondria (M ). X
806
J. Appl. Sci. Res., 3(9): 803-810, 2007
Fig. 16, 17: Photoelectron m icro graph o f pro ximal
convoluted tubules after 10 days of
treatment with low doses of sodium
selenite, showing cell necrosis (arrow)
with apical microvilla (head arrow),
condensed lysosmes (L), dense inclusion
body (D ), vacuo lated nuclei (N ),
degenerated mitochondria (M). X12000,
X12000 respectively.
Fig. 14: Photomicrograph of a semithin section of the
kidney cortex cells after 10 days of treatment
with sodium selenite (1 mg/kg body weight),
showing moderate degeneration with loss of
cellular detail architecture (head arrow) and
pyknosis nuclei (N). X1200.
Fig.15: Photomicrograph of a semithin section of the
kidney cortex cells after 10 days of treatment
with sodium selenite (2 mg/kg body weight),
showing more severe degeneration on the
tubular cells (head arrow) than the above
treated one (1 mg/kg body weight).
X1200.
these mitochondria are either hypertrophied and had
condensed matrices and also it was noticed in the
cytoplasm electro-dense inclusion body. T he nuclei of
some affected cells, showed shrinkage in size contain
many vacuoles and with chromatin clumped at the
nuclear membrane (Figs 16 & 17).
The distal convoluted tubules were swollen and
have electron lucent cytoplasm with few organelles as
degenerated mitochondria. The lumina of these tubules
were highly reduced (Fig.18).
T he
collecting
tubules,
showed
marked
degeneration, these cells have electron-dense cytoplasm
with few organelles. The nuclei have clumped
chromatin (Fig.19). After a higher dose (2mg/kg body
weight) of treatment, the proximal convoluted tubules
more affected than those in low doses. The microvilli
were broken and swollen mitochondria are often
disrupted. In severally damaged tubular cells,
vacuolization of the cytoplasm is observed and
the nuclei marked clumping of their chromatin
(Figs. 20 & 21).
The distal convoluted tubular cells and collecting
tubular cells showed more damage than those in low
folded in some areas and the dense mitochondria are
damaged (Fig. 13).
After 10 Days: Tubular cells affected by mild to
moderate degenerative lesions were scattered through
the cortex with loss of cellular detail and hydropic
degeneration after 10 days of treatment with lower and
higher doses of sodium selenite. The pathological
symptoms of these renal tubules were the loss of usual
cellular architecture, deterioration of cell membranes,
pyknosis of nuclei and necrosis of some cells in
tubular Lumina (Figs.14 & 15).
Electron microscopic examination of the section
from this subgroup revealed progressive degenerative
changes in renal tubular epithelium after 10 days for
lower and higher doses of treated groups.
The proximal convoluted tubules cells showed
coagulative necrosis, such cells were exceeding by
electron opaque and most of their organelles have been
obviously demolished except for some heavily
condensed lysosmes. The cytoplasm of these cells
contained many degenerated mitochondria. Some of
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J. Appl. Sci. Res., 3(9): 803-810, 2007
Fig. 18: Photoelectron micrograph of distal convoluted
tubules after 10 days of treatment with low
doses of sodium selenite, showing elongated
mitochondria (M), nucleus (N) and lumen (L).
X12000.
Fig.19: Photoelectron micrograph of collecting tubular
cells after 10 days of treatment with low
doses of sodium selenite, showing the
d eg en era tio n o f ce llular o rga nelles
mitochondria (M) and nucleus (N). X18000.
Figs. 20, 21: Photoelectron micrographs of proximal
convoluted tubules after 10 days of
treatment with high doses of sodium
selenite (2 mg/kg body weight), showing
cells degeneration, broken microvilli
(arrow) and nucleus (N). X9000, X12000
respectively.
mitochondria, whereas it is an inactive form in nuclei,
liposomes and peroxysomes [6 ]. Its activity increases in
the course of adding selenium to the diet.
Selenium both in excess and deficiency can exert
a pathogenic effect. An excess of this element,
especially in the form of inorganic compounds and
some of its metabolites, lead to changes similar to
those observed in the case of deficiency, i.e. to the
degeneration of free radicals, intensification of
lipid peroxidation
and even to
inhibition
of
synthesis of proteins [6 ].
Results of this study show that sodium selenite had
adverse effect on kidney cortex histology and
ultrastructure. Changes observed in the light microscope
occurred after treatment for 5 and 10 days with low
and high doses of sodium selenite.
During this study histological lesions were first
seen at 5 days. The types, distribution and progression
of light microscopic lesion observed in submicroscopic
ultrastructure studies showed great changes occurred in
proximal and distal convoluted tubular cells and
collecting tubular cells, dilation of the endoplasmic
reticulum, changes in the appearance of mitochondria
as well as lipososmes were observed. These are cellular
doses of treatment. The distal convoluted tubular cells
showed marked feature of degeneration, the apical
region of the cytoplasm are vacuolated and the swollen
dense irregular shape mitochondria are noticed and also
the nucleus of some cells showed clear signs of
pyknosis (Fig.22).
The lining cells of collecting tubules were marked
damaged. Their nuclei, showed pyknosis i.e. they were
small in size and darkly stained. And, also the apical
surface appeared smooth and protruded into the tubular
lumen and also the mitochondria are condensed and
irregular in shape (Fig.23).
Discussions: Selenium is an essential micronutrient in
all known forms of life. In humans, selenium is a trace
element nutrient which functions as cofactor for
reduction of antioxidant enzymes such as glutathione
peroxidases and thioredoxin reductase. Although in
large doses it caused toxicity. Glutathione peroxidase
is an active form occurs in cytosol and in the matrix of
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J. Appl. Sci. Res., 3(9): 803-810, 2007
and ultrastructural changes.
These results similar to that have been reported
after administration of sodium selenite for 10 days [1 8 ].
It has been reported that the effect of selenium
deficient on diet on two experimental models of
glomular diseases showed significant increased
reduction of glutathione peroxidase [1 ], thus indicating an
important role of glutathione peroxidase in the models
of glomular injury.
Similar resulted have been studied on the histology
of the rat kidney cortex after treatment with selenium
deficient diet for 1 to 12 weeks and found that
selenium deficiency induces protein urea and glucosuria
with renal
calcification,
which
may
be
primarily induced by injury of proximal tubule via
oxidative stress [1 0 ].
Also, the inhalation of selenium derivatives such as
dimethyl selenide has been associated with the tubular
injury of the kidney as swelling and vacillation of the
proximal tubules cells[3 ].
Similar histological examination of the renal
tubular cells, showed abnormalities in selenium
deficient, showed focal areas of tubular dilation,
atrophy and interstitial fibrosis [1 5 ].
Sloughing or internalization of the brush border
was noticed in this study and also has been reported by
other authors after treatment with different toxic
substances [5 ,1 3 ,2 0 ].
In summary, the results of this study demonstrate
that the oral administration of sodium selenite in rats
is kidney toxic as indicate by histopathological and
ultrastructual changes in the kidney cortex cells.
Fig. 22: Photoelectron micrograph of distal convoluted
tubules after 10 days of treatment with high
doses of sodium selenite, showing swollen
mitochondria (M), degeneration of the apical
region of the cell (arrow) and nucleus (N).
X12000.
Fig.23: Photoelectron micrograph of collecting tubular
cells after 10 days of treatment with high
doses of sodium selenite, showing damaged
cells with condensed mitochondria (M) and
apical dilation of the cell cytoplasm (arrow).
X12000.
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