Nickel induction of microsomal heme oxygenase activity in rodents

Conference · Sat Jan 01 00:00:00 EST 1983 · Toxicol. Appl. Pharmacol.; (United States)

OSTI ID:6241839

Sunderman, Jr, F W; Reid, M C; Bibeau, L M; Linden, J V

Heme oxygenase activity was measured in tissues of rats killed after administration of NiCl/sub 2/ or Ni/sub 3/S/sub 2/. Induction of renal heme oxygenase activity occurred 6 hr after NiCl/sub 2/ injection (0.25 mmol/kg sc), reached a maximum of five to six times the baseline activity at 17 hr, and remained significantly increased at 72 hr. Heme oxygenase activities were also increased in liver, lung, and brain at 17 hr after the NiCl/sub 2/ injection; heme oxygenase activities in spleen and intestinal mucosa were unchanged. The effects of NiCl/sub 2/ on heme oxygenase activities in kidney and liver were dose-related from 0.06 to 0.75 mmol/kg, sc. Three Ni chelators were administered (1 mmol/kg, im) prior to injection of NiCl/sub 2/ (0.25 mmol/kg, sc); d-penicillamine partially prevented Ni induction of renal heme oxygenase activity; triethylenetetramine had no effect; sodium diethyldithiocarbamate enhanced the Ni induction of renal heme oxygenase activity (three times greater than NiCl/sub 2/ alone). Intrarenal injection of Ni/sub 3/S/sub 2/ (10 mg/rat) caused induction of renal heme oxygenase activity at 1 week but not at 2, 3, or 4 weeks; no correlation was observed between induction of renal heme oxygenase activity and erythropoietin-mediated erythrocytosis. Hypoxia (10% O/sub 2/, 12 hr/day, 7 days) did not affect renal heme oxygenase activity. Induction of renal heme oxygenase activity was observed in mice, hamsters, and guinea pigs killed 17 hr after injection of NiCl/sub 2/ (0.25 mmol/kg, sc). These studies established (a) the time course, dose-effect, organ selectivity, and species susceptibility relationships for Ni induction of microsomal heme oxygenase activity, (b) the effects of Ni chelators, and (c) the lack of relationship between induction of renal heme oxygenase activity and the erythrocytosis that develops after intrarenal injection of Ni/sub 3/S/sub 2/.

• Research Organization: Univ. of Connecticut, Farmington
• OSTI ID: 6241839
• Report Number(s): CONF-820288-
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Vol. 68; Conference: 1. international conference on safety evaluation and regulation of chemicals, Boston, MA, USA, 24 Feb 1982
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GUINEA PIGS
SENSITIVITY
HAMSTERS
HEME
OXYGENASES
MICE
NICKEL COMPOUNDS
CARCINOGENESIS
TISSUE DISTRIBUTION
ORGANS
CHEMICAL ANALYSIS
ENZYME ACTIVITY
RATS
DOSE-RESPONSE RELATIONSHIPS
INJECTION
MICROSOMES
SPECIES DIVERSITY
ANIMALS
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
DISTRIBUTION
ENZYMES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTAKE
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
PATHOGENESIS
PIGMENTS
PORPHYRINS
RODENTS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
550200* - Biochemistry