Cadmium-induced alteration of drug action
Cadmium, a toxicologically important environmental contaminant, has been implicated as an etiological factor in a wide variety of pathological processes. Acute, intraperitoneal (i.p.) administration with cadmium can markedly alter the pharmacological response to a variety of drugs (hexobarbital, zoxazolamine, tremorine, and chlorpromazine) in the male rat. The threshold dose for this cadmium effect is 0.84 mg Cd/kg (i.p.) and the effect lasts at least 10 days with the peak effect occurring 2 to 5 days after cadmium. Mechanism studies reveal that the cadmium effect is the result of inhibition of hepatic drug metabolizing enzymes and not any alteration in end organ sensitivity to the drug. Treatment of male rats with cadmium prior to killing leads to a significant inhibition in the metabolism of hexobarbital, aniline, p-nitroanisole, zoxazolamine, and ethylmorphine, as well as reducing the microsomal cytochrome P-450 levels. Inhibition of the metabolism of these substrates by cadmium was also achieved when the metal was added in vitro to microsomes isolated from control rats. Pretreatment of rats with subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg, i.p.) prevented the previously observed alterations in drug action by the threshold cadmium dose. The apparent underlying basis for this protection phenomenon is the induction by cadmium of a hepatic metal-binding protein.
- Research Organization:
- Purdue Univ., West Lafayette, IN
- OSTI ID:
- 5204567
- Journal Information:
- Fed. Proc.; (United States), Journal Name: Fed. Proc.; (United States) Vol. 37:1; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BIOLOGICAL EFFECTS
CADMIUM
CASTRATION
CELL CONSTITUENTS
CHEMISTRY
CHRONIC INTAKE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
ENZYME INHIBITORS
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
KINETICS
MAMMALS
MEDICINE
METABOLISM
METALS
MICROSOMES
ORGANIC COMPOUNDS
ORGANOIDS
PHARMACOLOGY
PROTEINS
RATS
REACTION KINETICS
RODENTS
SEX DEPENDENCE
SURGERY
VERTEBRATES