الفهرس 
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Abstract
Cadmium is one of the important heavy metals which does not occur
naturally uncombined. It is a wide spread industrial product responsible for
acute and chronic poisoning in human and animals. It can contaminate air.
drinking water and food by pesticides galvanized pipes. cigarette smoking,
fertilization, oil and wood consumption as well as many other sources.
Cadmium has no beneficial biological functions in humans and is not
normally found in body fluids and tissues. Many researchers have reported
that Cd induces determinal effects on metabolism in a variety of tissues
resulting in nephropathy, liver damage, bony lesions, cardiovascular
diseases, emphysematous changes in the lung ..etc. On the other hand,
many studies revealed that cadmium is one of the important chemical
carcinogen to human as well as animals.
Hence, the present work was carried out to follow up the
histopathological and histochemical changes in the liver and kidney of rats
as well as the chromosomal aberrations in the bone marrow cells which
might be induced as a consequence of chronic cadmium exposing. This
trend aims principally to illustrate and evaluate any possible deleterious and
carcinogenic effects of this heavy metal.
Furthermore, the recovery signs from the possible toxic effects of
this heavy metal have been studied after its withdrawal or abstainance.
In the preliminary experiments the LDso of CdCI2 for subcutaneous
route of administration was determined using 40 rats and it has been equal
approximately 20 mgt kg. body weight.
A total number of 90 male white rats were used in the present
experiment, and the target organs comprise the liver (being the site of
detoxification), the kidney (the main target organ of chronic exposure) and
the bone marrow as the best tissue for stud·yingchromosomal aberrations.
The rats used in this study were divided into (3) groups, each
comprised (30) rats.
. A group of rats served as a control and were given equivalent
volumes of saline solution (NaC!).
The second group of rats was divided into five SUbgroups,four of
them were injected daily SUbcutaneouslywith a dose equaling 1/8 LOSOfor
10, 20, 30 and 45 days. The animals of the fifth SUbgroupwere injected in
the same way for 45 days and were left for 30 days after completion of
treatment to examine the recovery signs in the studied organs.
The third group of animals were treated by the same way with 1/4
LDso of CdCI2 and the animals were also examined after 10, 20, 30 and 45
days as well as the fifth subgroup were left for 30 days after 45 days of
treatment for studying the recovery signs due to cadmium withdrawal.
Small pieces of the liver and kidney were taken simultaneously from
both nontreated and treated rats and prepared for histological and
histochemical examination.
The bone marrow obtained extracted from the femora of all animals,
was prepared for chromosomal aberrations studies.
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Summary and Conclusion
The following results were obtained as a consequence of CdCI2
treatment.
The liver has displayed many lesions encountering distortion of the
normal architecture, cytoplasmic granularity, hydropic degeneration,
invasion of the portal areas and sinusoids and disruption of the cell
membranes.
Most of the portal and central veins were dilated and congested,
while the sinusoids revealed a marked obliteration. In addition nuclear
pyknosis and single cell necrosis were later manifested by many
hepatocytes. The longer time treated groups particularly those treated with
1/4 LDso of CdCI2 revealed severe damage of the liver tissue which was
characterized by ductal proliferation, severe karyorrhexis, karyolysis and
Von Kupffer cells hyperplasia as well as large focal areas of necrosis
A mild recovery, involving incomplete restoration of the normal liver
structure, was distincted by the 1/4 LDso treated rats examined 30 days
following cadmium withdrawal. Such recovery was more clarified in rats
administered with1/8 LD50 and treated in the same manner.
Glycogen has undergone a gradual diminution following
administration with the 1/8 and 1/4 LDso doses of CdCI2• These materials
were approximately disappeared on the 45-th day post- treatment with the
high dose.
A slight recovery of the glycogen picture was observed thirty days
after Cd withdrawal in rats previously treated with 1/4 LDso for 45 days; but
partial restoration of this material was detected in those cases treated
previously with the low dose.
Summary and Conclusion
DNA- containing particles displayed a mild increase in the livers of
each of the 1/8 and 1/4 LDso treated groups after 10 days. This pidure was
reversed and these inclusions gradually depleted, after 20 and 30 days from
the first injedion. Traces of DNA particles could be hardly detected on the
45-th day post Cd-administration, especially in the group of rats treated with
1/4 LDso.
A mild recovery in the DNA inclusions was manifested in the liver of
rats treated with 1/4 LDso and inspected 30 days after the abstainance of
CdCI2. But the clarified recovery was noticed in those previously injeeted
with the 1/8 LDso dose and left for the same period of time.
RNA inclusions of the hepatocytes of the rat also underwent a slight
increase in amount after 10 days of treatment with either of the 1/8 or 1/4
LDso doses. This picture started to be reversed and a slight decline seemed
to appear in these contents reaching the maximum depletion on the 45-th
day after Cd application particularly in those treated with the 1/4 LDso dose.
A partial restoration of the normal RNA levels was observed 30 days
following Cd withdrawal, in the livers of rats pre-treated with 1/8 LDso. But a
mild recovery was apparent also after 30 days in case of treatment with
1/4 LDso.
Total proteins displayed an increase in intensity in the liver cells
after 10 days of 1/8 and 1/4 LDso of CdCl2 administration. The longer time
treated groups revealed a gradual decrease in the total protein content
comparing to the control group and marked diminution in this inclusion was
noticed on the 45-th day post-1/4 LDso of CdC.2 administration.
Summary and Conclusion
Mild restoration of the total proteins was apparent 30 days post-Cd
withdrawal in the liver cells of rats treated with 1/4 LDso of CdCI2, whereas
such recovery partially observed, after 30 days in rats administered with
1/8 LDso.
The kidney:- Both of the applied doses 1/8 and 1/4 LDso were found
to exert marked histopathological and histochemical changes in the kidney
tissues.
Histopathologically, the highly affected member of the renal tissues
was the proximal convoluted tubules (PT), where their cells underwent
marked deterioration in their cytoplasm and nuclei. Pyknosis, karyorrhexis,
karyolysis, cytoplasmic swelling, single cell necrosis and tubular necrosis
were the marked pathological alterations, which have been manifested on
the 45th day post Cd-treatment with either the 1/8 and 1/4 LDso doses.
Other structures such as Bowman’s capsule suffered from negligible
changes in those groups treated for 10 and also 20 days. The marked
changes as hypercellularity of the capillary tuft and narrowing of the renal
space were observed after 45 days of the first injection. The distal
convoluted tubules (DT) as well as the collecting tubules underwent some
necrotic changes in their epithelial cells. Fibrosis was also observed in the
interstitial tissue in the longer time treated groups.
A partial recovery of the structure of the renal tissue was apparent in
the epithelial cells of the proximal tubules and renal corpuscles of rats
treated with 1/8 LDso and inspected 30 days following Cd abstinence. Mild
tissue repair was noticed after the same period in rats treated 1/4 LD50.
Polysaccharides. the renal tissues manifested a slight increase in
their amounts following administration of 1/8 and 1/4 LD50 of CdCI2 for 10
days. The basement membranes and the brush borders of the proximal
Summary and Conclusion
convoluted tubules as well as the capillary tuft cells were noticeably had
considerable amount of polysaccharides. Polysaccharides in general were
later on progressively diminished being remarkably absent on the 45th day
following Cd treatment, particularly with 1/4 LDso.
Indications of partial polysaccharides restoration were exhibited by
1/4 LOso, 30 days after Cd withdrawal. Such improvement was much more
marked in those given 1/8 LOso and also examined after 30 days following
the last injection.
DNA- containing particles exhibited a mild increase in the nuclei of
the cells of the proximal and distal convoluted tubules and mesangial cells
of the capillary tuft after treatment with 1/8 and 1/4 LOso doses of CdClz for
10 days. The groups administered for longer times revealed a gradual
decrease in this inclusion comparing to the normal case. This seemed to
continue in a progressive manner to the extent that the nuclei appeared
very feebly reactive for DNA particles on the 45th day after treatment with
particularly 1/4 LDso.
The recovery of the normal ONA-contentwas in a parallel correlation
with that in the protein case, where it was partially restored in those animals
treated with 1/4 LOso after 30 days of Cd- abstinence. But, it was more
obvious in the animals treated with 1/8 LDso and left for the same period of
time.
RNA particles have manifested an ascending abundance in the
cytoplasm and nucleoli of most cells of the renal tissue as a result of
administration of 1/8 and 1/4 LOu of CdClz for 10 days. Those inclusions
later on underwent a progressive diminution, which appeared particularly
prominent after 45 days of CdClz administration.
Summary and Conclusion
A mild restoration of the RNA content of the epithelial cells of the
proximal and distal convoluted tubules as well as the mesangial cells of the
capillary tuft occurred taken place in rats previously given 1/4 LDso and
inspected 30 days after CdCI2 withdrawal, whereas, treatment with 1/8 LDso
revealed a partial restoration of such inclusions after the same period of
time.
Total proteins were slightly increased in the epithelial cells of the
proximal convoluted tubules as well as the mesangial cells of the capillary
tuft, 10 days after administration of each of the low and the high doses of
CdCI2. This increase followed by a progressive diminution with the weakest
protein reactions remarkably distinct on the 45th day of Cd administration.
A partial recovery of protein material was observed 30 days after the
end of treatment in the epithelial cells of the renal tubules of rats previously
treated with 1/4 LDso, while it was much more marked after 30 days in case
of animals given 1/8 LDso of CdCI2.
DNA Image cytometry of hepatic cells demonstrated that the
normal hepatocytes have a regular multiplicity of normal diploid DNA
(euploid polyploidization). Chronic administration of CdCI2 manifested a
slight increase in the DNA- content of these cells after 10 days of treatment.
This picture was progressively reversed within the groups treated for a
longer time, where the maximum diminution of these inclusions
(hypodiploidy) was noted on the 45th day post 1/4 LDso application. The
hypodiploidy has been observed through the marked increase of the Gol G1
in those animals exposed to a long period of Cd administration.
The restoration of the normal DNA content of the hepatocytes was
weakly observed in the animals inspected 30 days after 1/4 LDso CdClz
abstainance. But, partial recovery was clearly appeared after the same
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Summary and Conclusion
period (30 days) in those animals previously treated with the low dose for 45
days.
DNA image cytometry of the kidney cells manifested the same
changes that observed in the liver cells except the alterations here were
markedly weak. The animals examined after 10 days of administration with
CdCI2 revealed a mild increase in the nuclear DNA content. On the other
hand, a gradual decrease was reported in the groups inspected 20 and 30
days following administration with each of the 1/8 and 1/4 LDso CdCI2. The
marked diminution of the total DNA content of these type of cells appeared
after 45 days of treatment with 1/4 LDso which illustrated by increase the
Go/G1 (quiescent state). Also, the DNA content of most cells was lower than
the normal diploid content (2C).
Photocytometry of the last groups treated with 1/8 LDso as well as
1/4 LDso and left 30 days post Cd abstainance revealed a partial recovery
and incomplete restoring of the normal diploid state.
Cytogenetic observations revealed incidence of structural and
numerical aberrations in the bone marrow cells which appeared in different
times following CdCb administration. Centromeric attenuation as well as
chromatid gaps were the early aberrations observed after 10 days of
administration with the low or the high doses. All of the structural
abnormalities including Centromeric attenuation chromosomal and
chromatidal gaps, fragments, deletion, acentric rings, discentric fusion and
beaded form were progressively observed in the following examined groups
and were then markedly apparent on the 45th day of Cd injection.
Hypoploidy was only the numerical aberration noticed in the longer time
treated animals was known as an aneuploid state, which predicts propability
of tumor incidence.
Summary and Conclusion
The repairing of these aberrations was slightly observed in the animals
treated with 1/4 LDso for 45 days and inspected 30 days following Cd
abstainance, while examination of the animals treated with 1/8 LDso and left
for the same period of time revealed a partial recovery and an obvious
repairing of the many chromosomal abnormalities. Hypoploidy was still
observed.
* In general, we can say that cadmium chloridehas beenproved to exert many
conspicuous effects on the liver and kidney of rats and many chromosomal
abnormalities in the bone marrow cells, which reflect its potential
carcinogenicity.
RECOMMENDATIONS
Finally we, recommend the following,
• The industrial companies, which extract Cd or use it in different
industrial processes, must take safety precautions to protect workers.
• Cigarette smoking must be prevented not only to reduce lung and
other cancers, but also to reduce mortalities from cardiovascular, nonmalignant
respiratory diseases and liver and kidney disorders.
• Superphosphate fertilizers must be slightly used or prevented in
agriculture.
• The safety precautions must be taken in consideration, when using
pesticides containing Cd.
• The galvanized pipes, which are used for transferring our drinking
water must be replaced by another healthy material.
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Summary and Conclusion
• Health education and periodic check to workers and citizens exposed
to Cd contamination must be done by applying the new techniques for
early detection of tumor using tumor markers imaging analysis.
• Further studies have been needed to evaluate and overcome the
hazardous effeds of the different compounds of Cd.