Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies.
Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.
Lewis
C P
CP
Laboratory of Lung Toxicology, Katholieke Universiteit Leuven, Belgium.
Demedts
M
M
Nemery
B
B
D000818:Animals; D002413:Cations, Divalent; D003035:Cobalt / Q000633:toxicity*; D006224:Cricetinae; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008647:Mesocricetus; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D014176:Protein Biosynthesis; D011700:Putrescine / Q000378:metabolism
D002413:Cations, Divalent; D003035:Cobalt; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005947:Glucose; D011700:Putrescine