Effects of acetaminophen on cadmium metabolism in mice

Journal Article · Sat Feb 01 00:00:00 EST 1986 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(86)90214-0· OSTI ID:5229722

Gale, G R; Atkins, L M; Smith, A B; Walker, Jr, E M; Fody, E P

Acetaminophen (ACM) administration to mice of the (C57BL/6 X DBA/2)F1 strain produced a typical hepatic centrilobular necrosis similar to that observed in rodents and humans. To determine the effects of this drug-induced necrosis on cadmium (Cd) metabolism, mice were given a sublethal dose of CdCl2 . 2.5 H2O containing 109CdCl2 and maintained for a period of time sufficient for Cd-metallothionein (Cd-MT) to be synthesized and distributed. Subsequent administration of ACM ip or po evoked a marked redistribution of Cd from livers to kidneys of mice, and increased the amount of Cd excreted in urine and feces. There were only minimal or no effects on Cd concentrations in other organs assessed. The effect of ACM on Cd redistribution was antagonized by administration of cysteine, a glutathione precursor, and was enhanced by pretreatment with phenobarbital, a potent inducer of the cytochrome P-450 mixed-function oxidase system. Pretreatment of mice with ACM 6 or 24 hr prior to Cd administration caused aberrations of the normal Cd distribution pattern, but no effect was noted when Cd administration was delayed for 48 hr after ACM injection, indicating recovery of the mechanisms of Cd-MT synthesis and sequestration. Sephadex G-75 gel filtration chromatography of serum from ACM-treated mice showed that most of the Cd was associated with high-molecular-weight proteins, and only a minor portion was present as Cd-MT. Cd excreted in urine was predominantly in a low-molecular-weight form, but there was evidence of two minor components of higher molecular weight, neither of which eluted as Cd-MT. Cd excreted in feces was insoluble following homogenization in 0.25 M sucrose solution. Cd in livers and kidneys of ACM-treated mice eluted as Cd-MT. Persons who have a moderately high Cd burden may be at risk of Cd nephrotoxicity if they incur hepatic necrosis subsequent to ACM abuse.

• Research Organization: Veterans Administration Medical Center, Charleston, SC
• OSTI ID: 5229722
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Vol. 2
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CADMIUM
EXCRETION
METABOLISM
TISSUE DISTRIBUTION
BODY BURDEN
CADMIUM 109
CHELATING AGENTS
CYSTEINE
DRUGS
FECES
KIDNEYS
LIVER
METALLOTHIONEIN
MICE
MIXED-FUNCTION OXIDASES
NECROSIS
PHENOBARBITAL
TRACER TECHNIQUES
AMINO ACIDS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AZINES
BARBITURATES
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
CADMIUM ISOTOPES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLEARANCE
DIGESTIVE SYSTEM
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ENZYMES
EVEN-ODD NUCLEI
GLANDS
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MATERIALS
METALLOPROTEINS
METALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PATHOLOGICAL CHANGES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RODENTS
THIOLS
VERTEBRATES
WASTES
YEARS LIVING RADIOISOTOPES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)