Lead has been used by mankind for more than 6,000 years because of its resistance to corrosion, its low melting point, and, ironically, sometimes for its sweet taste. Therefore, it is one the most studied environmental toxins, and its toxicity has been known for more than 2,500 years. The major exogenous sources and associated pathways of lead exposure are lead-based paint, the combustion of leaded gasoline, occupational exposure in lead-related industries, lead-contaminated water or food, and industrial and mining activities. Both children and adults are susceptible to health effects from lead exposure, although the typical exposure pathways and effects are somewhat different. Children who live in houses that were built before 1978 and adults who are occupationally exposed are at greatest risk. Lead mining, lead smelting, and use of leaded gasoline are common in many developing countries, where children and adults may receive substantial lead exposure. Effects in children generally occur at lower blood lead levels than in adults (Table 1) because children are more sensitive to lead exposure in a given environment due to their behavior and physiology.
Because of the high hand-to-mouth activity of infants and young children, absorption of lead is estimated to be as much as 5 to 10 times greater in them than in adults. Most human exposure to lead occurs through ingestion or inhalation. Lead exposure in the population occurs primarily through ingestion, although inhalation may be the major contributor for workers in lead-related occupations. Gastrointestinal absorption of lead in children is increased with dietary deficiencies of iron, calcium, zinc, and vitamin C. After it enters the human body, the absorption and biological pathways of lead depend on a variety of factors. Especially important determinants are the physiologic characteristics of the exposed person, including nutritional status, health, and age, along with the type and level of lead exposure.
Table 1 Toxic Effects of Lead at Various Concentrations in Children and Adults
Lead primarily affects the peripheral and central nervous system, kidneys, red blood cells, and calcium metabolism. It can also cause hypertension, reproductive toxicity, and developmental effects. The blood lead levels associated with encephalopathy in children vary from study to study, but levels of 70 to 80 µg/dl or greater appear to indicate a serious risk. Even without encephalopathy symptoms, these levels can create problems. Although it is often impossible to determine the effects of low blood lead through clinical examination, the developing nervous system of children can be affected adversely with less than 10 µg/dl of lead in the blood. Lead exposure may cause low IQ levels, poor classroom performance, greater absenteeism, reading disabilities, and deficits in vocabulary, fine motor skills, and reaction time. It can also affect hand-eye coordination in young adults more than 10 years after childhood exposure.
Acute, high-level lead exposure has been associated with hemolytic anemia. In chronic lead exposure, lead induces anemia by interfering with heme biosynthesis and by diminishing red blood cell survival. Lead’s impairment of heme synthesis can affect other heme-dependent processes in the body outside of the hematopoietic system, including neural, renal, endocrine, and hepatic pathways.
Chelating agents are drugs that bind with heavy metals in the bloodstream, causing them to be discharged from the body in urine and bile. They can be effective at reducing the total body lead burden and acute toxicity effects in individuals with high blood lead levels. However, because of the risk for potentially harmful effects of the chelating agents and the remobilized lead, chelation therapy is generally not recommended for individuals with blood lead levels below 45 µg/dl.
A change in the pro-oxidant-to-antioxidant ratio in favor of the former, because of the production of reactive oxygen species (ROS) by mitochondria, defines oxidative stress. The effects of redox active metals on ROS production have been known for years. However, the theory of lead’s ability to induce oxidative stress as a redox inactive metal has begun to gain support during the past 10 years. Lead-induced oxidative stress has led scientists to study the protective qualities of antioxidants against lead toxicity, along with their possible chelating abilities. Nevertheless, the use of antioxidants in conjunction with chelating agents as a therapeutic strategy has not been thoroughly investigated.
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