212
[47]. Another important pathway of lead intake is gastrointestinal absorption and
retention but it depends upon the chemical environment of gastrointestinal lumen
and iron stored in GIT [57].
Lead-Induced Oxidative Stress
Lead induces oxidative stress by interfering with many biochemical processes
(Fig. 13.5). Lead has the ability to mimic or inhibit the calcium action by interacting
with proteins. The biological molecules that are bound with lead, have not the ability to perform a number of biochemical processes. Lead has the ability to bind with
sulfhydryl group and amide group present in enzymes, as a result, alter the configuration of enzymes and diminish the activity of enzymes. Lead also interferes with
the transport of some cations by exhibiting the competition with other metallic cations for binding with the active site of enzymes [5]. This oxidative damage of membrane induced by lead is due to a change in fatty acids composition present in the
membrane [59].
The lipid peroxidation induces oxidative stress and the production of reactive
oxygen species in the lipid membrane. These free radicals abstract the electron from
lipids that are present in the membrane and cause oxidative damage to the cell membrane. The free radicals are also responsible for the oxidation of hemoglobin and the
destruction of red blood cells. The oxidation of lipids and hemoglobin results due to
inhibition of δ-aminolevulinate dehydratase(ALAD), the substrate level of
δ-aminolaevulinic acid (ALA) is increased in the blood and urine. The generation of
superoxide and hydrogen peroxide results due to the elevated level of ALA. These
oxides and peroxides react with oxyhemoglobins and hydroxyl radicals generated
[60]. Lead has the ability to form a covalent bond with sulfhydryl group of antioxidant enzymes such as glutathione (GSH) and causes inactivation of this enzyme.
The level of GSH is decreased which is not compensated by a γ-glutamyl cycle that
is also responsible for the synthesis of GSH from cysteine [61]. Lead has the ability
to bind with an enzyme ALAD, glutathione peroxidase (GP X ), glutathione reductase,
and glutathione-S-transferase, causes inactivation of these enzymes, as a result,
depresses the level of GSH [62]. Due to exposure of lead, alteration in gene expression occurs. The mechanism that is involved in alteration of gene expression is
binding of lead with DNA associated protein, protamine, by interaction with zincbinding site [63].
Lead has the ability to interact with enzymes that catalyze the synthesis of vitamin D and involve in the maintenance of the cell membrane. Lead disintegrates the
cell membrane and RBCs with a membrane that has no integrity become fragile and
results in anemia [64]. Lead also affects glucose-6-phosphate dehydrogenase, the
enzyme responsible for catalyzing the initial step in the pentose phosphate pathway.
Lead enhances the level of this enzyme in RBCs in human beings [58].
K. Irshad et al.
[47]. Another important pathway of lead intake is gastrointestinal absorption and
retention but it depends upon the chemical environment of gastrointestinal lumen
and iron stored in GIT [57].
Lead-Induced Oxidative Stress
Lead induces oxidative stress by interfering with many biochemical processes
(Fig. 13.5). Lead has the ability to mimic or inhibit the calcium action by interacting
with proteins. The biological molecules that are bound with lead, have not the ability to perform a number of biochemical processes. Lead has the ability to bind with
sulfhydryl group and amide group present in enzymes, as a result, alter the configuration of enzymes and diminish the activity of enzymes. Lead also interferes with
the transport of some cations by exhibiting the competition with other metallic cations for binding with the active site of enzymes [5]. This oxidative damage of membrane induced by lead is due to a change in fatty acids composition present in the
membrane [59].
The lipid peroxidation induces oxidative stress and the production of reactive
oxygen species in the lipid membrane. These free radicals abstract the electron from
lipids that are present in the membrane and cause oxidative damage to the cell membrane. The free radicals are also responsible for the oxidation of hemoglobin and the
destruction of red blood cells. The oxidation of lipids and hemoglobin results due to
inhibition of δ-aminolevulinate dehydratase(ALAD), the substrate level of
δ-aminolaevulinic acid (ALA) is increased in the blood and urine. The generation of
superoxide and hydrogen peroxide results due to the elevated level of ALA. These
oxides and peroxides react with oxyhemoglobins and hydroxyl radicals generated
[60]. Lead has the ability to form a covalent bond with sulfhydryl group of antioxidant enzymes such as glutathione (GSH) and causes inactivation of this enzyme.
The level of GSH is decreased which is not compensated by a γ-glutamyl cycle that
is also responsible for the synthesis of GSH from cysteine [61]. Lead has the ability
to bind with an enzyme ALAD, glutathione peroxidase (GP X ), glutathione reductase,
and glutathione-S-transferase, causes inactivation of these enzymes, as a result,
depresses the level of GSH [62]. Due to exposure of lead, alteration in gene expression occurs. The mechanism that is involved in alteration of gene expression is
binding of lead with DNA associated protein, protamine, by interaction with zincbinding site [63].
Lead has the ability to interact with enzymes that catalyze the synthesis of vitamin D and involve in the maintenance of the cell membrane. Lead disintegrates the
cell membrane and RBCs with a membrane that has no integrity become fragile and
results in anemia [64]. Lead also affects glucose-6-phosphate dehydrogenase, the
enzyme responsible for catalyzing the initial step in the pentose phosphate pathway.
Lead enhances the level of this enzyme in RBCs in human beings [58].
K. Irshad et al.