Comparative effects of cadmium, zinc, and lead in vitro on pulmonary, adrenal, and hepatic microsomal metabolism in the guinea pig

Journal Article · Sun Nov 01 04:00:00 EST 1981 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398109530125· OSTI ID:5731176

Colby, H D; Johnson, P B; Zulkoski, J S; Pope, M R; Miles, P R

The in vitro effects of Cd, Zn, and Pb on pulmonary, adrenal, and hepatic microsomal enzyme activities in guinea pigs were compared. Cd and Zn produced concentration-dependent (20-200 ..mu..M) decreases in benzphetamine demethylase and biphenyl hydrozylase activities in adrenal, liver, and lung. Pb had no significant effect on either enzyme in any of the tissues studied. Adrenal and pulmonary enzymes were more sensitive to the effects of Cd and Zn than were hepatic enzymes. Benzo(a)pyrene hydroxylase and ethoxycoumarin demethylase activities were decreased by Zn, Cd and Pb in adrenal, liver, and lung microsomes. The inhibitory effects on benzo(a)pyrene and ethoxycoumarin methabolism were far greater than those on benzphetamine or biphenyl metabolism. The relative potencies of the metals as inhibitors of xenobiotic metabolism were Zn > Cd > Pb. Cd and Zn also inhibited steroid 21-hydroxylase activity in adrenal microsomes, but Pb had no effect on steroid metabolism. In addition, microsomal epoxide hydratase activity in adrenal, liver, and lung was inhibited by Cd but not by Zn or Pb. The results demonstrate that adrenal and pulmonary microsomal enzyme, like those in liver, are inhibited by various metals. Inhibition of mixed-function oxidases by metals in vitro is apparently not related to changes in cytochrome P-450 levels or substrate binding to cytochrome P-450. In addition, the actions of Cd, Zn, and Pb in each tissue are highly dependent on the substrates employed.

• Research Organization: West Virginia Univ. School of Medicine, Morgantown
• OSTI ID: 5731176
• Journal Information: J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 8:5-6; ISSN JTEHD
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADRENAL GLANDS
ANIMALS
BIOLOGICAL EFFECTS
BODY
CADMIUM
CELL CONSTITUENTS
COMPARATIVE EVALUATIONS
DIGESTIVE SYSTEM
ELEMENTS
ENDOCRINE GLANDS
ENZYME ACTIVITY
GLANDS
GUINEA PIGS
IN VITRO
INHIBITION
LEAD
LIVER
LUNGS
MAMMALS
METABOLISM
METALS
MICROSOMES
ORGANOIDS
ORGANS
PATHOLOGICAL CHANGES
RESPIRATORY SYSTEM
RODENTS
VERTEBRATES
ZINC