Oxidative mechanisms in the toxicity of chromium and cadmium ions.
Chromium and cadmium are widely used industrial chemicals. The toxicities associated with both metal ions are well known. However, less information is available concerning the mechanisms of toxicity. The results of in vitro and in vivo studies demonstrate that both cations induce an oxidative stress that results in oxidative deterioration of biological macromolecules. However, different mechanisms are involved in the production of the oxidative stress by chromium and cadmium. Chromium undergoes redox cycling, while cadmium depletes glutathione and protein-bound sulfhydryl groups, resulting in enhanced production of reactive oxygen species such as superoxide ion, hydroxyl radicals, and hydrogen peroxide. These reactive oxygen species result in increased lipid peroxidation, enhanced excretion of urinary lipid metabolites, modulation of intracellular oxidized states, DNA damage, membrane damage, altered gene expression, and apoptosis. Enhanced production of nuclear factor-kappaB and activation of protein kinase C occur. Furthermore, the p53 tumor suppressor gene is involved in the cascade of events associated with the toxicities of these cations. In summary, the results clearly indicate that although different mechanisms lead to the production of reactive oxygen species by chromium and cadmium, similar subsequent mechanisms and types of oxidative tissue damage are involved in the overall toxicities.
Stohs
S J
SJ
Department of Pharmaceutical Sciences, Creighton University School of Pharmacy and Allied Health Professions, Omaha, NE 68178, USA.
Bagchi
D
D
Hassoun
E
E
Bagchi
M
M
D000079:Acetaldehyde / Q000652:urine; D000096:Acetone / Q000652:urine; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002840:Chromates / Q000008:administration & dosage / Q000633:toxicity; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000652:urine; D016158:Genes, p53 / Q000502:physiology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000652:urine; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency
D002412:Cations; D002840:Chromates; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D002104:Cadmium; D002857:Chromium; D000096:Acetone; D005557:Formaldehyde; D008315:Malondialdehyde; C016104:sodium bichromate; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D000079:Acetaldehyde; D019256:Cadmium Chloride