important factor in absorption. In addition, membranous barriers influence
translocation of any chemical from the exterior of a cell to the intracellular
fluid of a cell within an animal. A toxicant that gains entry by the mouth must
pass from the gastrointestinal tract to the circulation and then to the cell. Such
a process involves a series of translocation steps and increases the possibility of
exposure of the chemical to large endogenous molecules, such as proteins,
which may effectively bind and therefore functionally change and remove the
offending chemical.
Certain chemicals, however, may react with membrane material, such as
proteins, thus altering the membrane structure. For example, heavy metals
such as Pb, cadmium (Cd), and Hg may react with the –SH groups on
membrane protein molecules. Similarly, the lipid constituent of the membrane
may be altered by peroxidation by O 3 , as mentioned previously. Free radicals
formed in the reaction may attack not only lipids but also proteins, leading to
disruption of the membrane.
7.2.4 LIVER
The liver, the largest solid organ of the body (Figure 7.3), is an incomparable
chemical plant. As discussed in Chapter 4, the liver plays the foremost role in
detoxifying xenobiotics. In addition, it is a blood reservoir and a storage organ
for some vitamins, and for digested carbohydrate (as glycogen), which is
broken down releasing glucose to sustain blood sugar levels. The liver is also a
manufacturing site for enzymes, cholesterol, proteins, vitamin A (from
carotenoids), blood coagulation factors, and other molecules.
Although the liver is noted for its ability to regenerate (under certain
conditions), it can nevertheless be severely damaged. For example, cirrhosis (a
chronic progressive disease of the liver that is characterized by an excessive
formation of connective tissue, followed by hardening and contraction), which
is related to alcoholism and poor nutrition, may be caused by chronic exposure
to chemicals such as carbon tetrachloride (CCl 4 ). Another liver disease is
fibrosis, characterized by the deposition of excessive amounts of collagen such
that the features of the hepatic lobules are accented. Hepatic fibrosis can result
from repeated exposure or continuous injury following prolonged low-level
exposure to environmental chemicals. Portal fibrosis with portal hypertension
has also been reported in humans repeatedly exposed to As
1 compounds or
vinyl chloride.
2,3
7.2.5 KIDNEYS
The kidneys (Figure 7.5) are the principal organs for excretion of both
endogenous and exogenous toxins. Approximately one fourth of the blood
pumped by each beat of the heart passes through the kidneys. The kidneys
incessantly filter various substances from the blood, reabsorb some of them,
and concentrate wastes created by metabolic processes in urine. Optimal
mechanisms for excretion depend on selective conservation of essential
Defense Responses to Toxicants
105
[16:53 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-007.3d]
Ref: 4365 MING-HO YU Chap-007 Page: 105 99-110
translocation of any chemical from the exterior of a cell to the intracellular
fluid of a cell within an animal. A toxicant that gains entry by the mouth must
pass from the gastrointestinal tract to the circulation and then to the cell. Such
a process involves a series of translocation steps and increases the possibility of
exposure of the chemical to large endogenous molecules, such as proteins,
which may effectively bind and therefore functionally change and remove the
offending chemical.
Certain chemicals, however, may react with membrane material, such as
proteins, thus altering the membrane structure. For example, heavy metals
such as Pb, cadmium (Cd), and Hg may react with the –SH groups on
membrane protein molecules. Similarly, the lipid constituent of the membrane
may be altered by peroxidation by O 3 , as mentioned previously. Free radicals
formed in the reaction may attack not only lipids but also proteins, leading to
disruption of the membrane.
7.2.4 LIVER
The liver, the largest solid organ of the body (Figure 7.3), is an incomparable
chemical plant. As discussed in Chapter 4, the liver plays the foremost role in
detoxifying xenobiotics. In addition, it is a blood reservoir and a storage organ
for some vitamins, and for digested carbohydrate (as glycogen), which is
broken down releasing glucose to sustain blood sugar levels. The liver is also a
manufacturing site for enzymes, cholesterol, proteins, vitamin A (from
carotenoids), blood coagulation factors, and other molecules.
Although the liver is noted for its ability to regenerate (under certain
conditions), it can nevertheless be severely damaged. For example, cirrhosis (a
chronic progressive disease of the liver that is characterized by an excessive
formation of connective tissue, followed by hardening and contraction), which
is related to alcoholism and poor nutrition, may be caused by chronic exposure
to chemicals such as carbon tetrachloride (CCl 4 ). Another liver disease is
fibrosis, characterized by the deposition of excessive amounts of collagen such
that the features of the hepatic lobules are accented. Hepatic fibrosis can result
from repeated exposure or continuous injury following prolonged low-level
exposure to environmental chemicals. Portal fibrosis with portal hypertension
has also been reported in humans repeatedly exposed to As
1 compounds or
vinyl chloride.
2,3
7.2.5 KIDNEYS
The kidneys (Figure 7.5) are the principal organs for excretion of both
endogenous and exogenous toxins. Approximately one fourth of the blood
pumped by each beat of the heart passes through the kidneys. The kidneys
incessantly filter various substances from the blood, reabsorb some of them,
and concentrate wastes created by metabolic processes in urine. Optimal
mechanisms for excretion depend on selective conservation of essential
Defense Responses to Toxicants
105
[16:53 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-007.3d]
Ref: 4365 MING-HO YU Chap-007 Page: 105 99-110