Oxidative stress induced by lead, cadmium and arsenic mixtures: 30-, 90-, and 180-day drinking water studies in rats
Whittaker, MH; Lipsky, M; Wang, G; Chen, X; Fowler, BA
Lead, cadmium, and arsenic warrant continued scrutiny because all three are found at 95% of Superfund sites. Moreover, they are associated with adverse health effects such as cancer and nephrotoxicity. Oxidative stress is thought to play a major role in the development of adverse health effects from exposure to these trace elements, and may occur through the generation of free radicals due to the accumulation of aminolevulinic acid (ALA) and free iron. In order to investigate mechanisms of trace element-induced oxidative stress, 8 groups of male Sprague-Dawley rats were exposed to deionized water, single trace elements (Pb (25 ppm as lead acetate), Cd (10 ppm as cadmium chloride), As (5 ppm as sodium arsenite)), or element mixtures for 30-, 90-, or 180-days. These doses were selected from a series of dose-response studies at LOEL dose levels. After 30 days, urinary ALA (mg/day) was increased in all groups compared to control (+18%-+287%). After 90 days, urinary ALA was increased in 6 groups (+15%-+52%). After 180 days, urinary ALA was increased in 4 groups (+25%-+77%). Urinary iron (?g/day) was decreased in all groups after 30 days (-8%?50%); after 90 days urinary iron was increased only in the Pb and As groups (+12%-+17%). After 180 days, urinary iron was decreased in all test groups (-3%?30%). When expressed in units of ?g Fe/ml urine, urinary iron was increased in 4 of the 7 groups after 30 days (Pb, PbxCd, CdxAs, PbxCdxAs)(+14%-+77%); after 90 days, iron was increased in 6 of the 7 groups (all except PbxAs)(+10%-+30%); and after 180 days, iron was increased in 3 of the 7 groups (PbxAs, CdxAs, PbxCdxAs)(+8%-+30%). These data indicate that ALA and iron accumulate after acute exposure to trace elements or their mixtures. The accumulation of these two oxidative stress precursors appears to level off over 180 days, suggesting that some type of adaptation to oxidative stress occurs following repeat exposures to trace elements or their mixtures