Antioxidant nutrients and lead toxicity
Introduction
Lead is a ubiquitous environmental and industrial pollutant that has been detected in almost all phases of environmental and biological systems. The quantity of lead used in the 20th century far exceeds the total consumed in all previous eras. This heavy use has caused local and global contamination of air, dust, and soil. Lead is known to induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory animals and humans (Goyer, 1996, Ruff et al., 1996), including central and peripheral nervous systems (Bressler et al., 1999), haemopoietic system (De Silva, 1981), cardiovascular system (Khalil-Manesh et al., 1993), kidneys (Humphreys, 1991), liver (Sharama and Street, 1980) and male (Lancranjan et al., 1975) and female reproductive systems (Rom, 1980).
Generation of highly reactive oxygen species (ROS), such as superoxide radicals (O2−), hydrogen peroxide (H2O2), hydroxyl radicals (OH) and lipid peroxides (LPO), in the aftermath of heavy metal ions are known to damage various cellular components including proteins, membrane lipids and nucleic acids (Halliwell and Gutteridge, 1989). Evidence indicates that transition metals, especially iron and copper, are able to produce ROS that result in lipid peroxidation, DNA damage, and depletion of cell antioxidant defense systems. The more recent finding of the oxidative damage caused by lead exposure of biological macromolecules suggested a new mechanism for an old problem. One current theory as to how lead exerts its toxic effects suggests that lead-induced oxidative stress contributes to the pathogenesis of lead poisoning by disrupting the delicate prooxidant/antioxidant balance that exists within mammalian cells (Lima-Hermes et al., 1991, Monterio et al., 1995). Some in vitro studies pointed to increased production of ROS after lead treatment (Ribarov and Bochev, 1982, Monterio et al., 1991). In vivo studies suggested that lead exposure might cause generation of ROS and alteration of antioxidant defense systems in animals (Lawton and Donaldson, 1991, Sandhir et al., 1994, Hsu et al., 1997) and workers (Ito et al., 1985, Solliway et al., 1996).
This review summarizes studies on lead-induced oxidative stress as well as the beneficial role of antioxidant nutrients on such stress. It will focus especially on reproductive toxicity and consider new work on the molecular genetic mechanisms of lead toxicity, and examine recent animal studies and epidemiological findings.
Section snippets
The mechanisms for lead-induced oxidative stress
An imbalance in the generation and removal of ROS in tissue and cellular components is known to cause damage to membranes, DNA, or proteins, and is generally called oxidative stress. The mechanisms for lead-induced oxidative stress include the effect of lead on membrane, DNA, and antioxidant defense systems of cells. On cell membrane, the presence of double bonds in the fatty acid weakens the CH bonds on the carbon atom adjacent to the double bonds and makes H removal easier. Therefore, fatty
Dose–response between lead exposure and oxidative stress
In pregnant women with low-levels of blood lead concentrations from 2.7 to 12.6 μg/dl, an inverse relationship was observed between blood lead levels (BLL) and serum levels of α-tocopherol and ascorbic acid (West et al., 1994). Blood levels of MDA, a product of lipid peroxidation, were strongly correlated with lead concentrations higher than 35 μg/dl (Bechara et al., 1993). From low to high doses of lead exposure, there were different responses of lead-induced oxidative stress in various target
Beneficial role of antioxidant nutrients on lead-induced oxidative stress
Oxidative stress can be partially implicated in lead toxicity. Therefore, reducing the possibility of lead interacting with critical biomolecules and bolstering the cell's antioxidant defenses might be associated with the beneficial role of antioxidant nutrients through exogenous supplementation of antioxidant molecules (Table 2). Although mechanisms of antioxidant nutrients being effective via rebalancing the impaired prooxidant/antioxidant ratio in abating lead toxicity are still not
Conclusion
Generation of highly reactive oxygen species in the aftermath of lead exposure may result in systematic mobilization and depletion of the cell's intrinsic antioxidant defenses. When formation of reactive oxygen intermediates outstrips the scavenging capacity of these antioxidant defense mechanisms, harmful free radicals accumulate and increase the likelihood of oxidative damage to critical biomolecules, such as enzymes, proteins, DNA, and membrane lipids. Several mechanisms have been proposed
Acknowledgements
This review was supported in part by the grants NSC89-2314-B-327-001 and NSC90-2621-Z006-005 from National Science Council, Republic of China.
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