General Mechanism of Toxicity
Lead toxicity is usually occurred by generating an increased amount of reactive oxygen species (ROS) and by interfering with an antioxidant generation . Lead is not a redox-active element and it cannot directly play a role in those reactions which initiate the ROS formation. It was found that the generation of ROS in erythrocytes is increased by the interaction of lead with oxyhemoglobin . The most significant contribution of lead in the initiation and expansion of oxidative stress is arisen by its interference with the enzymes and other cellular components/mechanisms of the defensive system which are responsible for preventing oxidative damage . Glutathione (GSH), a tri-peptide of cysteine, histidine, and glutamate, is one of the most significant elements that protects cell components from ROS damage . In healthy cells and tissues, 90% of GSH exists in reduced form and 10% in oxidized form, and it usually functions as an antioxidant defense mechanism. GSH after being converted (oxidized) to glutathione disulfide is reduced back to GSH by glutathione reductase . Lead inactivates glutathione by binding to GSH’s sulphydryl group, which inhibits sulphydryl-dependent enzymes (e.g., glutathione reductase, superoxide dismutase, catalase, etc.) and causes GSH replenishment to become inefficient. Inhibition of these enzymes leads to the production of reactive oxygen species with resultant oxidative stress. The increase in oxidative stress leads to the damage of the cell membrane because of lipid peroxidation. Lead obstructs the activities of 5-aminolevulinic acid dehydratase and directs to hemoglobin oxidation, which together with the lipid peroxidation can cause hemolysis .
Lead enters the intravascular space and rapidly binds to red blood cells. The estimated half-life of lead in the blood is 30days. Lead from the blood diffuses into the soft tissues, such as the brain, bone marrow, liver, kidneys, etc. Then this heavy metal diffuses into bone and remains deposited there for a longer period of time where its half-life is of several decades. Increased bone turnover with pregnancy, lactation, menopause, or immobilization causes the rise of blood lead levels  (Figure 21.1).
Figure 21.1 Induction of lead toxicity by promoting oxidative stress and increased levels of reactive oxygen species [2,17].