Analysis of lung damage induced by trichloroethylene inhalation in mice fed diets with low, normal, and high copper content.
Copper is both an essential nutrient required for the activity of several enzymes and a toxic element able to catalyze free radical formation. Trichloroethylene (TCE) is a xenobiotic that generates epoxidic intermediates by bioactivation through the cytochrome P-450 system. In this study, the influence of a dietary copper imbalance on the TCE-induced lung damage was investigated. Weaning mice were fed copper-deficient, copper-sufficient, and copper-excessive diets. After 4 wk, mice were exposed for 30 min to 6,500 ppm of TCE and euthanatized 48 hr later. Lung damage in the TCE-treated mice consisted of vacuolations of Clara cells and was quantitatively evaluated by counting the vacuolated cells per micrometer of basal lamina. At the ultrastructural level, vacuolations appeared as the result of hydropic swelling of the endoplasmic reticulum cisternae. The copper-deficient mice presented the highest number of vacuolated Clara cells. These mice also showed alteration of the capillary endothelium and interstitium and decreased pulmonary copper-zinc-superoxide dismutase activity. Occurrence of oxidative stress in lungs of both copper-sufficient and copper-deficient mice following TCE treatment was indicated by a decrease in reduced glutathione and an increase in its oxidized form.
Giovanetti
A
A
Section of Toxicology and Biomedical Sciences, ENEA CR Casaccia, Rome, Italy. giovanetti@casaccia.enea.it
Rossi
L
L
Mancuso
M
M
Lombardi
C C
CC
Marasco
M R
MR
Manna
F
F
Altavista
P
P
Massa
E M
EM
D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage* / Q000633:toxicity; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012997:Solvents / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D014241:Trichloroethylene / Q000633:toxicity*
D000975:Antioxidants; D012997:Solvents; D014241:Trichloroethylene; D003300:Copper; D013482:Superoxide Dismutase; D005978:Glutathione