Effects of Vitamin C on Lead Induced Developing Thymus in Mice: A review

Universal Journal of Environmental Research and Technology
All Rights Reserved Euresian Publications (c) 2011 eISSN 2249 0256
Available Online at: www.environmentaljournal.org
Volume1, Issue 2: 91-102




Open Access





Review Article

Effects of Vitamin C on Lead Induced Developing Thymus in Mice: A review

1Sharma R. and *1Kantwa S. M.

1 Developmental and Environmental Toxicology Research Laboratory Department of Zoology, University
College of Science, Mohanlal Sukhadia University, Udaipur, (Rajasthan) 313001

*Corresponding Author Email Address: phd10_sanwarmal@mlsu.ac.in
Abstract:
The present review deals with effects of vitamin C on lead intoxicated developing thymus in mice .In the
world of environmental health and medicine, lead exposure remains one of the most important problems in
terms of prevalence of exposure and public health impact. Previous research has shown that every level of
lead exposure is dangerous to animals and humans. Thus lead toxicity continues to be a leading
environmental issue. Little is known about the persistent Immunotoxic effect of Pb when administered
during specific stages of embryonic development. A variety of toxic effects caused by lead exposure during
gestation and lactation have been reported in human and animal studies. Our immune system is our most
powerful weapon against disease. Fetal and early postnatal life represents critical periods in vertebrate
immune system development. Disruption of such development by Immunotoxic chemical exposure has been
widely described in experimental animal model. The available animal data suggest the potential immune
function in humans exposed immunotoxicants during fetal and early postnatal life. Administration of
vitamin C results in improvement in several components of human immune response. Vitamin C regulates
the immune system because of its antioxidant properties and its role in collagen synthesis required for
stabilization of epithelial barriers. It plays a role in phagocytic function and has an immunostimulatory effect
on lymphocyte cells. Limited information is available regarding the possibility of inhibited postnatal immune
capacity in humans as a result of pre and postnatal immunotoxicant exposure. To fulfill this lacuna an
attempt has been taken to gather the significant information on deformities in immune system due to
immunotoxicant exposure during pre and postnatal development.

Keywords: Lead, Thymus, Postnatal, Immunotoxicity, Vitamin C

1.0 Introduction:

The natural environment is necessary for the
Lead is the metal, which has been associated with
existence of present and future generation
human activities from the past. Levels of lead
(Bogner, et al., 2008; Andrew, et al., 2007) and has
content in various media have been coupled with
provided all the basic needs of human societies
data for lead intake and absorption in the human
thought history (Smith and Curnus, 2008). Lead
body, for both children and adults are affected not
remains a significant occupational and public
only morphologically but also anatomically and
health problem. Despite decades of research, lead
histologically. Various organs also show critical
toxicity also remains one of the most studied
damage (Pizzol, et al., 2010). The general
subjects of all with in the fields of environmental
population could be significantly exposed owing to
health and medicine. The majority of the
poorly glazed ceramic ware, food canning, battery
industries associated with high lead exposure have
cosmetic and mining industry, contaminated water
made advances in their control of occupational
by lead and motor vehicle deposition. It was an
exposure. However, cases of unacceptably high
important cause of morbidity and mortality during
exposure and even of frank lead poisoning are still
the Industrial Revolution and effective formal
seen, predominantly in the demolition and tank
control of lead workers did not occur until the
cleaning industries. Modern research findings
pioneering occupational health work of Lane
indicate that lead may be toxic at levels previously
(1949). In view of the long history of lead's toxicity
thought to have no harmful effects. In most
and the extensive publications one would think
industries blood lead levels have come down
that lead exposure is controlled up to a major
below levels at which signs or symptoms are seen
extent and lead poisoning was merely a historical
and the current focus of attention is on the sub-
entity. Unfortunately, this is not the case; there
clinical effects of exposure. Inevitably there is
are still industries in this country where clinical
pressure to reduce lead exposure in the general
lead poisoning occasionally still occurs (Levin, et
population and at work places, but any legislation
al., 1997).
must be based on a genuine scientific evaluation

of the available evidence (Gidlow, 2004).
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2.0 Effect of Lead on the Body:
impairment. Lead inhibits enzyme, alters cellular
In spite of continuously exposure to lead and
calcium metabolism, and stimulates synthesis of
absorption through various routes it has no known
binding proteins in kidney, brain and bone, and
biological function in the body, and is highly toxic
slowdown nerve conduction. Less severe exposure
and accumulates in various tissues of human body
to lead, designated by blood lead levels, has been
such as bone, blood, kidney, liver and thymus
implicated in poor pregnancy outcome, impaired
(Baldwin and Marshall, 1999). Peoples have known
neurobehavioral development, reduced stature in
about the poisonous effects of lead from 200BC.
young children, and higher blood pressure in
The lead has been used comprehensively for both
adults. Acute high lead exposure can cause serious
industrial and domestic applications for hundreds
physiological effects. Effects of lead exposure vary
of years. As exposure to lead in work places and in
according to exposure, timing and levels, and
the environment is profoundly regulated now,
other factors, and some effects may be latent. The
there are few cases of acute lead poisoning. The
pathological effects of lead on the renal, nervous,
first deliberation of toxicity is exposure of an
reproductive, endocrine, and immune systems
organism to a toxic substance. The major routes of
have been reviewed. Emphasis is placed on
accidental or intentional exposure to toxicants by
reported subclinical effects due to chronic, low-
humans and other animals are the skin, the lungs
level lead exposure. The crucial issue of whether
(inhalation, respiration, pulmonary route), and the
subtle
behavioral,
intellectuals,
and
mouth (oral route). The way by that a toxic
developmental impairment occurs in young
substance is introduced into a complex system of
children, as a result of lead-induced CNS damage is
an organism is strongly dependent upon the
discussed in detail. This issue remains unresolved.
physical and chemical properties of the substance.
Further studies are needed in order to determine
Lead have both physical and chemical properties
the long-term health effects of continuous, low-
to enter and affect the human body A man
level lead exposure (Damstra, 1977).
exposed to lead not only at work places, but also

from lead based paint in older housing and from
Little is known about the effects of lead on
soil, that is still persists in the community. From
reproductive
performance
and
postnatal
the perspective of human reproduction, lead is
development
following
chronic,
low-level
known
to
cause
a
number
of
adverse
exposure. Kimmel, et al., (1976) exposed female
consequences in both men and women. Effects in
rats chronically to lead acetate via the drinking
women include infertility, miscarriage, premature
water (0.5, 5, 50, 250 ppm) from weaning through
membrane rupture, pre-eclampsia, pregnancy
mating, to lactation. Vaginal opening was delayed
hypertension and premature delivery (Winder,
1-2 weeks but estrous cycle and pregnancy rates
1993).
were normal in those females that are exposed to

50 and 250 ppm lead. No teratogenic effects and
Lead in the blood has a half-life of around 25 days
no significant increase in fetal resorption were
and in tissue its half-life is about 40 days (Hu,
observed, although exposure to 250 ppm lead
1998; Williams, et al., 1999). Due to this, blood
acetate caused a slight, but no significant increase
lead levels are not very useful as an indicator of
in fetal resorptions. The lead-treated animals
how-much lead exposure an individual has
produced litters of normal numbers, but the
undergone, as they only show recent exposure
offspring from the 50 and 250 ppm groups
(Timbrell, 1995; Williams, et al., 1999). However,
weighed less at weaning and showed delays in
in bone lead has a half-life of 25 years or more,
physical development. Reiter, et al., (1975) also
and it is possible to estimate past exposure to lead
observed developmental delays in rat offspring
by X-ray (Agency for toxic Substances and Diseases
exposed to 50 ppm lead from gestation to
Registry, 1997). Lead is excreted from the body
lactation. Whether these delays in development
mainly in the urine, but also in the feces, and small
were the result of a direct effect of lead on the
amounts also appear in hair, nails, sweat, and
nervous system of the pups or reflect secondary
saliva and breast milk. By these exposure media
changes (malnutrition, hormonal imbalance, etc.)
lead enters in the body and causes hematological,
is not clear. Whatever the mechanisms involved,
gastrointestinal, and neurological dysfunction in
these studies do suggest that low-level chronic
adults and children. Young children are particularly
exposure to lead might induce postnatal
affected by lead poisoning as they absorb greater
developmental delays.
amounts from the gastrointestinal tract. Severe or

prolonged exposure may also cause chronic
Several studies in animal models have suggested
nephropathy, hypertension, and reproductive
that lead may interfere with various aspects of the
immune response. Lead has been reported to
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result in an increased susceptibility to infection in
rate and magnitude of thymus dependant
mice and rats. Various factors may be involved in
immunological function.
producing this enhanced susceptibility to infection.

Smith et al., (2008) results show that dietary lead
3.1 Normal Anatomy:
concentration did not affects body weight gain and
Located in the upper part of the thorax, the
food consumption but there are significant
thymus is quite large in the young animals, but as
increase in fecal lead concentration and total fecal
the animal grows, the gland atrophies. The
lead output. There work also shows dose depend
mammalian thymus is located in the mediastinum,
increase in tissue lead concentration. Jiao et al.,
anterior to the major vessels of the heart, and
(2010) also reported that there were no significant
ventral to the base of the heart and aortic arch,
differences in body weight of control and lead
with variable extension of one or both lobes into
treated animals but continuous exposure of lead
the cervical region in the rat (Haley, 2003). In mice
increase blood lead levels in all treated animals. A
thymus is situated anterior to the pericardial
significant increase in the serum alkaline
membrane. The thymus consists of two distinct
phosphate activity and increase in the level of
lobes. A connective tissue named isthmus, connect
serum bilirubin content indicate serious hepatic
the both lobe of the thymus. Each lobe is covered
damage if lead is exposed for 7 days. Hemoglobin
by a thin connective tissue capsule and in most
also decreased due to above treatment because of
species lobes are divided into several lobules of
breakdown of haemoglobin in its downstream
different shape, size and orientation. There is no
products or because the process of hemoglobin
sublobulation in the mouse. Evidence for a
biosynthesis may have been affected (Kilikdar et
functional cervical thymus in mice has been
al., 2011). Sharma et al., (2011) also demonstrated
reported (Terszowski, et al., 2006).
that lead exposed swiss albino mice show the loss

of body weight and significant decrease in RBC
3.2 Histology:
count, WBC count, Hb level and serum total
Thymus is partly an endocrine gland and partly a
protein count. Animal also show the increase in
lymphoid structure. According to various lymphoid
serum
alanine
transaminase,
aspartate
organs the thymus is histologically most consistent
aminotransferase, and creatinine and cholesterol
in different animal species. It is an epithelial organ.
level. Lead, a common environmental contaminant
It's each lobule divided into two regions outer one
that has no known beneficial or desirable
is cortex and inner one is medulla. Cortical region
nutritional effect, has been found to produce a
is dense to epithelial cell in comparison to
wide range of adverse effects that involve several
medullary region. Both regions are separated by a
organic systems and biochemical activities (Patrick,
vascular region named corticomedullary zone. The
2006).
epithelial cells form an open framework containing

predominantly T lymphocytes, smaller populations
3.0 Thymus Development:
of B lymphocytes and plasma cells and scattered
Most embryological evidence at present favours
populations of other cells such as endocrine cells.
the view that the thymic epithelium is derived
It is divided into a morphologically distinct cortex
from both the ectoderm and the endoderm of the
and
medulla
separated
by
a
vascular
third and the fourth branchial grooves and
Corticomedullary zone. The medulla also contains
pharyngeal pouches. The rodent thymus develops
reticular cells and the unique "Hassall's Corpuscle"
from the endoderm of the 3rd and 4th pharyngeal
which are spherical structures composed of
pouches and surrounding mesenchyme (Dijkstra
concentric layers of spindle shaped cells whose
and Sminia, 1990). As development progresses,
function is unknown.
the thymus along with the thyroid and

parathyroid, sharing the same pharyngeal pouch
3.3 Epithelial Stroma:
origin, migrate caudally. They separate around day
The bulk of the supporting framework in the
15 when the thymus migrates into the thorax.
thymus is composed of the network of epithelial-
Embryonic thymic remnants can give rise to
reticular cells (Banks, 1993). Epithelial cells in the
ectopic thymic tissue in the neck, thyroid and
subcapsular region of the thymus form one or two
parathyroid glands (Suster and Rosai, 1992). The
cellular layers. In the outer cortex and ensheathing
thymus is the first of the lymphoid organs to be
blood vessels, epithelial cells are thin and sheet
formed and grows immediately after birth in
like, but elsewhere they assume a stellated
response to postnatal antigen stimulation and the
appearance. Epithelial cell populations differ in
demand for large numbers of mature T cells.
structural characteristics, antigen expression and
Genetic factors also influence the age of onset,
the hormone synthesis capacity. These cells are
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divided into four subcategories, sub capsular
lymphocyte are larger, mature, well stained and
cortical cells, inner cortical cell, medullary cells and
have more cytoplasm in this region comparison to
Hassalls
corpuscles
on
the
basis
of
cortical region T-lymphocyte.
immunohistochemical techniques (DeWaal, et al.,

1997). Number of antigenic epithelial population is
3.8 The Corticomedullary Ratio:
decrease
with
the
age
of
mice.
More
The area of cortex and medulla is known as
immunohistochemical studies are provided by
corticomedullary ratio. Early in life cortex is large
Greaves (2000); Kuper, et al. (1995); and Suster
in comparison to medulla it means ratio is more
and Rosai, 1992).
than one but later in life (after involution) cortex

decrease
and
medulla
increase
than
3.4 Capsule:
corticomedullary ratio decrease (less than one)
Each lobe of thymus is covered by a thin capsule
(Elmore, 2006). Therefore we can say that
which divides the lobe of thymus in several lobules
corticomedullary ratio depended upon the age of
of different size and orientations by septae.
animal. Tryphonas, et al., (2004) provided
Capsule is made up by outer collagen fiber layer
morphometric
measurements
of
histological
and inner reticular fiber layer and occasionally in
sections of the thymus in control Sprague-Dawley
between, clusters of lymphocytes are found.
rats. By their method, the average cortico-
Supporting framework of thymus is made up by
medullary ratio was determined to be 4.4 to 4.7
epithelial reticular cells network (Bruijntjes, et al.,
(30 and 90 day-old males) and 3.9 to 6.3 (30- and
1993; Elmore, 2006).
60 day-old females).


3.5 Cortex:
In the cortex, massive numbers of densely packed
small lymphocytes predominate, occupying the
interstices of the epithelial reticulum, which in
histological sections largely obscure and forming
about 90% of the total weight of thymus.
Thymocytes undergo mitosis in all cortical zones as
the clones of differentiating T cells mature,
gradually
moving
deeper
in
the
cortex.
Histologically, the darkly staining cortex contains
densely packed, small, immature lymphocytes; in
the sub capsular cortex region there are some
active lymphocytes found which have a round to
oval nucleus with one or two well known nuclei
and basic cytoplasm. A slope of small but active

Fig. A: Photomicrograph of thymus shows cortex
cell comes from the outer cortex to the
and medulla composed of epithelial cells. At this
corticomedullary junction.
stage more epithelial cells are present in cortical

region in comparison to medullary region. (Original
3.6 Corticomedullary Junction:
magnification, x 10; hematoxylin and eosin stain).
Corticomedullary
junction
is
composed
by

overflowing blood vessels, slight perivescular
connective tissue and mature and immature T-
4.0 Thymic involution:
lymphocytes. Arterioles of overflowing blood
As we know, the thymus is a lymphoid organ; it
vessels are divided into capillaries and extend into
develops gradually parallel to other organs till
cortical and medullary region. In this region B-
puberty. After puberty several changes occur in its
lymphocyte and plasma cells are also found which
morphology and cellularity. This phenomenon is
increase with the age of animal.
known as thymic involution. During thymic

involution cortical and medullary region reduce;
3.7 Medulla:
there is also a decrease in number of cortical
lymphocytes and increase in tangible body
The central part of the lobule which has less
macrophages. In histological view involution is
epithelial cells density in comparison to cortex is
reduction
in
the
size,
decrease
cortical
known as medulla. In this region we found the
lymphocyte, irregular cortex and demarcation of
more mature T-lymphocyte, well known epithelial
corticomedullary zone, increase the perivescular
cell, Hassalls corpuscles, mixed macrophages,
space, perivascular B lymphocyte and plasma cells.
immature B-lymphocytes and few myoid cells. T-
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There are multiple pathways involved in lead
The thymus body ratio is greatest perinatally but
effects on male reproductive system. It is unclear
the organ continues to increase in absolute size
that lead affect gonads directly or through the
until about puberty, after which it tends to
disruption of reproductive hormones. But it is
gradually decline. According to Kuper, et al.,
known that high level of lead decrease the sperm
(2002) when there is a decrease in thymic size and
count
and
motility,
including
abnormal
cellularity one should use the term "reduce
morphology (Vigeh, et al., 2011). Greenstein, et
number of cortical lymphocyte and increase
al., (1987) showed that orchidectomy restored the
number of macrophages". These changes may be
thymus and raised the total white cell count in 18-
identified as "atrophy or involution". Normal
month-old rats in which the thymus had virtually
development, histology, and function of the
disappeared. Similar thymic regeneration was
thymus have been reported previously (Kuper, et
achieved in intact old rats with subcutaneous
al., 1992; Pearse, 2006). The use of standardized
implants
of
luteinizing
hormone
releasing
descriptive nomenclature with respect to thymic
hormone. The activity of the thymus appears to be
pathology is addressed (Haley, et al., 2005;
related to the levels of thymic hormones in the
Elmore, 2006).
organs. With aging the functional capacity of the

thymus may be reduced or not effectively
4.1
Nonproliferative
Morphological
stimulated but it is not completely lost.
Changes in the Thymus Factors Effecting

Species, strain and sex differences have significant
Thymic Cellularity:
role in the involution of thymus. There is no
A direct correlation exists between thymic
species in which complete involution takes place,
microenvironment and developing T cells. Multiple
there is always some remnants of thymus at every
factors and conditions result in an alteration in the
stage of life (Khosla and Ovalle, 1986). Strain
cellular density and cellular composition of the
differences can also be important. For example,
thymus. Most commonly recognized is a decrease
aged brown Norway female rats thymus contain
in lymphocytes resulting from a range of
mostly epithelial cord with less lymphocytes but
background physiological influences and the
Wister or WAG strain's female has scarcer
immunosuppressive
effect
of
xenobiotics.
epithelial components (Kuper, et al., 1990).
Inadequate nutrition, social stress also affects
According to our study on Swiss mice, as seen in
thymic involution. The histological appearance of
fig. A developing thymus lobules are not well
the thymus under these varied conditions is
separated and the number of epithelial cell in
similar, since the end point is the reduction in
cortical region is more than medullary region but
cortical lymphocytes, and shrinkage of the thymic
in case of adult there are numerous epithelial cells
lobules (Schuurman, et al., 1994). During
in cortical region. There is more space in between
involution there is an increase the number of
the developing epithelial cells in comparison to
apoptotic bodies, tangible body macrophage and
adult.
lymphocyte depletion. After involution medulla

has a higher cellular density than the cortex.
5.0 Effects on Developing Thymus:
Factors
such
as
stress
and
toxicity
can
The increasing awareness of environmental
simultaneously be superimposed on the normal
pollution has led to a parallel renewal of interest in
ageing
process
of
lymphocyte
reduction.
metals as potential immunotoxicants. Recently
Consequently, the distinction between atrophy
there has been an increased concern about the
and involution in older animals can be
accumulation of lead in the environment. Lead,
problematic.
today, remains an
economically important

commodity. It is highly reactive and forms
4.2 Age Associated Effects/Involution:
numerous compounds with very different physical
Animals age play an important role in the level of
and chemical properties, e.g. solubility that affects
cellularity of the thymus and its overall histological
their bioavailability. One of the major soluble lead
changes. Physiological involution reflects the
compounds is lead acetate trihydrate. It is used as
change in function of the thymus from lymphocyte
a penetrating agent in cotton dyes, in antifouling
production to recirculation. In rodent thymus
paints and insecticides, as a lead coating for
develops gradually parallel with gonads but after
metals, as a drier in paints, varnishes, pigment
puberty or gonadal development it decreases in
inks, as a colorant in hair dyes and as a processing
size. It may be due to increased circulating levels
agent in the cosmetics, perfume and toiletry
of sex steroid hormones. Gonads play a role in
industries (IARC, 2004). The primary routes of
thymic involution in both sexes (Grossman, 1985).
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potential exposure to it are ingestion, inhalation or
at pre and postnatal developmental on low and
dermal contact and it is absorbed about 1.5 times
high levels of exposure. Even low dose of lead
faster than any other lead compound.
exposure at early age critically affects on

developing T-cell in thymus (Schuurman, et al.,
During development, migration and maturation of
1994).
Immunotoxic
reactions
commonly
T-cell a synchronized set of events occur. The basic
immunosuppression (Gopinath, 1996) is defined
needs and required microenvironment for the
by selective or general depression in lymphoid
differentiation and maturation of these cells is
organ. In this view several studies show the
provided by primary lymphoid organ. In mice
relation of thymus and lead through which lead
thymus is a primary lymphoid organ where T-cells
decrease the thymus body weight ratio. However
under goes the maturation and differentiation
high dose of lead exposure decreases food and
process,
while
B-cell
maturation
and
water
consumption
and
increases
stress.
differentiation takes place in red bone marrow.
Therefore thymus body weight ratio is not a
These cells are colonized in thymus and bone
criterion to show the immunosuppression. In some
marrow around day 13, continuing until birth
cases a dose-response relationship as well as
(Dietert, et al., 2000; Medlock, et al., 1984). After
changes in other lymphoid tissues may be of some
undergoing "thymic education" within thymus, the
help in deciding whether thymic atrophy is a direct
T-lymphocyte matures into immunocomptent
effect of immunosuppression or nonspecific
cells, which are then read to encounter foreign
response to stress (Greaves, 2000).
antigens. Graham et al., (2011) studies focus that

oral exposure of lead in Sprague Dawley female
The thymus is sensitive to immnotoxicants and
rats alters the organ body weight ratio, most
show the decreasing size and apoptosis of cortical
notably of the thymus weight. Lead is a heavy
lymphocytes. A histological change depends upon
metal and defines as a xenobiotic agent and shows
the dose of immunotoxicant. Following apoptosis
the developmental immunotoxic effects. Adverse
of cortical lymphocytes and their removal by
effect occurs in offspring's immune system when
macrophages, a decrease in cortical cellularity, loss
lead is exposed through full gestation (Bunn, et al.,
of
the
cortex
and
blurring
of
normal
2001a; Chen, et al., 1999; Faith, et al., 1979;
corticomedullary demarcation are seen. Recent
Luster, et al., 1978; Miller, et al., 1998).
studies show that low levels lead exposure have

considerable impact not only on neurological
Lewin, et al., (1999) reported that Pb levels near
(Verstraeten, et al., 2008) but also on immune
four super sites had mean dust Pb levels of
system (Dietert and Piepenbrink, 2006; Farrer, et
1108mg/kg and soil Pb levels were associated with
al., 2008). Other studies show that the lead
blood Pb levels in children. In addition to Pb
intoxication affects humoral immune activities,
exposure levels, blood-lead levels measured for 2
function of lymphocyte, cytokine production
day at end of exposure in the dams coincided with
(McCabe, et al., 2001), diminishes host resistance
blood-lead levels (Rojas, et al., 2000; Fischbein, et
(McCabe,
et
al.,
1999),
cause
increased
al., 1993; Sata, et al., 1998). Therefore human
susceptibility to infections, autoimmune diseases
exposures to Pb at these levels still exist. Lead
and allergy (Bernier, et al., 1995; Colombo, et al.,
acetate is an important immunotoxicant for the
2004). T-cells are also targeted by lead
phagocytic cells, humoral and cell mediated
immunotoxicity (McCabe, et al., 1999; Razani-
immunity. The mechanism by which it affects
Boroujerdi, et al., 1999). Therefore we can say that
these cells is not understood. (Institoris, et al.,
lead contribute in immunosuppression of all
1999; Bunn, et al., 2001; Dietert, et al., 2004;
animals. Razani-Boroujerdi, et al (1999) in vivo
Bishayi & Sengupta, 2006). Its immunosuppressive
studies also show the enhance lymphocyte
effect may cause an increased susceptibility of
proliferation activity. Therefore further studies are
exposed individuals to infection, infestation or the
required for finding the mechanism of lead action
occurrence of tumors.
by which it affects the animal and its immune

system.
6.0 Immunotoxicity:

Immune system is affected by any physical
Although several mechanisms have been proposed
chemical or other agents are known as
to explain the toxic effects of lead, the exact
immunotoxicity (Koller, 1987) and the agent by
mechanism is still not clear. One mechanism is
which toxicity caused is known as immunotoxicant.
that this metal interacts with renal membranes
Lead is a well known immunotoxicant which
and enzymes and disrupts energy production,
affects the maturation of T-lymphocyte in thymus
calcium metabolism, glucose homeostasis, and ion
transport processes (Tsuruoka, et al., 2000).
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Another suggested mechanism is by inducing
8.0 Effects of Vitamin C on Lead
apoptotic cell death as apoptosis induced by lead
Intoxicated Developing Thymus:
in several types of cells has been reported, such as
The antioxidant might play a role in the treatment
in cerebellar neurons (Oberto, et al., 1996) and
of lead poisoning (Gurer, et al., 2001).Vitamins like
midbrain dopamine neurons (Tavakoli-Nezhad, et
C and E are capable to control the critical balance
al., 2001). Nevertheless, the exact mechanism of
of oxidants and antioxidants in the body. Jiao et
apoptosis induced by lead is not clear and needs to
al., (2010) reported that natural antioxidant
be studied especially in vivo (Zhang, et al., 2004).
treatment reduce the blood lead level by metal ion
Teijon, et al., (2010) studies show that oral
chelating mechanism. There work also show that
administration of lead in the form of lead acetate
addition of vitamin C and natural antioxidant
cause intense affects on thymus and a double
reduce the absorption of lead in lead treated
behavior for the proliferation index. When a
animals. Simon and Hudes (1999) reported that
control group of animals are compared with lead
intake of ascorbic acid decrease the blood lead
treated group than proliferation stimulation is
level and control the lead toxicity. Some previous
observed. So it shows that lead exposure to animal
work also reviewed the immune enhancing role of
increase the proliferation of thymic lymphocyte.
vitamin C (Wintergerst, et al., 2006; Webb, et al.,

2007; Strohle and Hahn, 2009; Thomas and Holt,
7.0 Study of Lymphocyte Subpopulations:
1978). Due to its antioxidant properties and
Teijon, et al., (2010) work showed that oral
collagen synthesis role it contributes in regulation
exposure of lead cause a double behavior for the
of immune system (Jacob, et al., 1991). So oral
proliferation
index.
During
intraperitoneal
intake of vitamin C improve the immune system
exposure same effects occur. Therefore both
components
such
as,
leucocytes
function,
routes of lead exposure induce the T-lymphocyte
neutrophil and monocyte movement (Lavine et al.,
proliferation. Apoptotic reactions also continue in
1994), natural killer cell activity, lymphocyte
the thymus if lead is exposed to rats. So, these
proliferation and chemotaxis (Jacob, et al., 1991;
data corroborate that lead, although it has
Panush, et al., 1982).
influence on mechanisms of cell proliferation, does
Gajawat et al., (2005) studied on prophylactic use
not activate calcium-dependent endonucleases,
of ascorbic acid against radiation and heavy metal
unlike other environmental pollutants such as
intoxication. They reported that prophylactic use
dioxins, which activate this enzymatic system
of vitamin C is quite effective during lead
(Kaioumova, et al., 2001). It has not been observed
intoxication
and
irradiation.
By
increasing
that significant necrosis has been generated in
sulphydryl groups and glutathione level of blood,
thymocytes due to lead. Nevertheless, the
vitamin C protects the biological system.
structural alterations produced in thymus indicate

that it does significantly affect the functionality of
Vitamin C is effective in protecting against
this tissue.
oxidative damage in tissues and also suppresses

formation of carcinogens like nitrosamines. There
The
investigation
of
regulation
processes
is an inverse relationship with blood pressure and
maintaining tissue homeostasis in the thymus
both plasma vitamin C and Vitamin C. Vitamin C
showed a significant increase in apoptosis, a
has a lowering effect on blood pressure, especially
decrease in cellular proliferation and a decrease in
on systolic pressure more than a diastolic
thymic export as indicated by a reduction in the
pressure. Low levels of plasma vitamin C are
number of recent thymic emigrants (RTE) in the
associated with stroke and with an increased risk
peripheral blood. The proliferative response of
of all cause mortality. Increased consumption of
mature thymocytes to Concanavalin A (ConA) was
ascorbic acid raises serum ascorbic levels and
also significantly reduced in socially defeated rats.
could decrease the risk of death (Walingo, 2005).
The strong positive relationship between total
Mega doses of vitamin C increase the levels of
thymocyte numbers and peripheral RTE numbers
antibody that fights against germs and viruses in
and the long-lasting atrophy of the thymus in
both stressed and unstressed rats, with greater
defeated
animals
may
suggest
negative
antibody
increase
in
the
unstressed
rats
consequences for the heterogeneity of naive T
(Unknown, 1999). Stressed animals may need
cells in the peripheral T cell pool after social stress
larger vitamin C doses for proper function of the
(Engler and Stefanski, 2003).
immune system. Ali, et al., (2010) noticed that

hematological parameters were reduced due to

lead acetate-treatment but when Vitamin C was
given along with lead the values tend to be normal
97
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Universal Journal of Environmental Research and Technology

at 14 days which suggest that Vitamin C is a good
2. Ali, F., Singh, K., Rani, S., Ahirwar, V. and Khan,
antioxidant is overcome lead toxicity. Furthermore
S. (2010): Effect of Ascorbic acid Against Lead
vitamin C was shown to improve the human
(Pb) Toxicity. IJPSR., 1: 81-85.
immune response such as antimicrobicidal natural
3. Andrew, H., Brainard, M. D. and Brislen, H. C.
killer cell activities, lymphocyte proliferation and
(2007): Viewpoint: Learning Professionalism: A
chemotaxis (Heuser and Vojdani, 1997; Campbell,
view from the Trenches. Acad. Med., 82:
et al., 1999; Wolf, 1993; pavlovic, et al., 2005;
1010-1014.
pavlovic and pavlovic, 2005; pavlovic, et al., 2004)
4. Baldwin, D. R. and Marshall, W. J. (1999):
indicating the important role of this vitamin in
Heavy Metal Poisoning and its Laboratory
regulating the immune response.
Investigation. Ann Clini Biochem., 36: 267-300.

5. Banks,
W.
(1993):
Applied
Veterinary
9.0 Conclusions:
Histology. Mosby, St. Louis.
*
6. Bernier, J., Brousseau, P., Krzystyniak, K.,

On the basis of above literature we can say
Tryphonas, H. and Fournier, M. (1995):
that thymus develops gradually from 12th day
Immunotoxicity of Heavy Metals in Relation to
of gestation to puberty.
*
Great Lakes. Environ Health Perspect., 103:

After puberty dramatically retrogressive
23-34.
changes occurs in its size and cellularity. This
7. Bishayi, B. and Sengupta, M. (2006):
phenomena known as thymic involution or
Synergism in Immunotoxicological effects due
age associated thymic atrophy. The potential
to Repeated Combined Administration of
effects of early exposure to lead on thymic
Arsenic
and
Lead
in
Mice.
Int.
development have been not characterized.
*
Immunopharmacol., 6: 454 - 464.

In the above review we tried to evaluate the
8. Bogner, J. et al., (2008): Mitigation of global
capacity of lead to alter thymus development
greenhouse gas emissions from waste:
in neonatal pups following gestational and
conclusions
and
strategies
from
the
lactational exposure.
*
intergovernmental panel on climate change

The results of various studies suggest that
(IPCC). Fourth Assessment Report. Working
lead can directly influence the development of
Group III (Mitigation). Was. Manag. Res., 26:
thymus and functioning of thymocytes. Since,
11-32.
thymulin levels may influence lead induced
9. Bruijntjes, J. P., Kuper, C. F., Robinson, J. E.,
Immunotoxicity. The embryonic endocrine
and Schuurman, H. J. (1993): Epithelium-free
status may be an important consideration.
Area in the Thymic Cortex of Rats. Dev.
* Lead affects on thymus cellularity and
Immunol., 3: 113-22.
maturation process of T-lymphocyte. Many
10. Bunn, T. L., Ladics, G. S., Holsapple, M. P., and
investigations shows that we can treat the
Dietert,
R.
R.
(2001a):
Developmental
lead induced Immunotoxicity by several
Immunotoxicology Assessment in the Rat:
antioxidants like vitamin C. The immune
Age, Gender and Strain Comparisons after
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detoxification
role
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free
radical
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treatment are proved by the literature.
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* Further studies are required to evaluate the
Windows
of
Embryonic
Development:
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Differential Immunotoxic outcome based on
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