Zinc suppression of free radicals induced in cultures of rat hepatocytes by iron, t-butyl hydroperoxide, and 3-methylindole

Journal Article · Sat Oct 01 04:00:00 EDT 1988 · Proc. Soc. Exp. Biol. Med.; (United States)

DOI:https://doi.org/10.3181/00379727-189-42786· OSTI ID:6600463

Coppen, D E; Richardson, D E; Cousins, R J

The effect of zinc on lipid peroxidation initiated by either ferric-nitrilotriacetate, t-butyl hydroperoxide, or 3-methylindole was studied using primary monolayer cultures of rat liver parenchymal cells. The malondialdehyde content of the cells and culture medium was used to estimate the extent of lipid peroxidation. As the zinc concentration of the culture medium was increased from 1 to 48 microM, peroxidation was diminished. Cellular zinc and metallothionein levels were proportionally increased by supplemental zinc. Zinc supplementation of the medium inhibited NADPH-cytochrome c reductase activity and stimulated glutathione peroxidase activity. The uptake of iron into the hepatocytes was significantly reduced as the level of zinc was raised, suggesting that zinc antagonizes uptake of chelated iron into isolated hepatocytes and in this way blocks iron-induced peroxidation. Furthermore, induction of metallothionein synthesis by zinc may contribute to the reduction in free radicals. Spectra from electron spin resonance studies, using phenylbutylnitrone as a spin-trapping reagent, demonstrated that free radical production was inversely related to the zinc concentration of the culture medium. Spin trap data suggest that metallothionein added to lysed cells in vitro decreases free radical production. Studies using the spin trap, 3,3,5,5-tetramethylpyrroline-N-oxide indicated that cumulatively the predominant radical present in the cultures was a phenyl radical with hydroperoxide or methylindole. Collectively, our data demonstrate that zinc inhibits free radical production and lipid peroxidation in cultured hepatocytes. The mode of action of zinc could occur via free radical scavenging by zinc-induced metallothionein and/or by processes related to cytochrome P-450 and glutathione peroxidase.

• Research Organization: Univ. of Florida, Gainesville (USA)
• OSTI ID: 6600463
• Journal Information: Proc. Soc. Exp. Biol. Med.; (United States), Journal Name: Proc. Soc. Exp. Biol. Med.; (United States) Vol. 189:1; ISSN PSEBA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZOLES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
ELECTRON SPIN RESONANCE
ELEMENTS
ENZYME ACTIVITY
ENZYMES
HETEROCYCLIC COMPOUNDS
INDOLES
IRON
LIPIDS
LIVER CELLS
MAGNETIC RESONANCE
MAMMALS
METABOLISM
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
PROTEINS
PYRROLES
RADICALS
RATS
RESONANCE
RODENTS
SOMATIC CELLS
SYNTHESIS
TRANSITION ELEMENTS
VERTEBRATES
ZINC