Inhibition of diquat-induced lipid peroxidation and toxicity in precision-cut rat liver slices by novel antioxidants
The ability of the novel antioxidants U-74,006F and U-78,517G and a known antioxidant (N,N'-diphenyl-p-phenylenediamine, (DPPD)) to inhibit chemically induced (diquat dibromide) oxidative stress was examined in precision-cut liver slices. Previous studies in rat liver microsomes demonstrated th...
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Published in | Toxicology and applied pharmacology Vol. 108; no. 2; p. 321 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.04.1991
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Subjects | |
Online Access | Get more information |
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Summary: | The ability of the novel antioxidants U-74,006F and U-78,517G and a known antioxidant (N,N'-diphenyl-p-phenylenediamine, (DPPD)) to inhibit chemically induced (diquat dibromide) oxidative stress was examined in precision-cut liver slices. Previous studies in rat liver microsomes demonstrated the ability of these antioxidants to inhibit lipid peroxidation without preventing redox cycling of diquat. Diquat (1 mM) initiated lipid peroxidation in liver slices prepared from F344 rats. A 30-min preincubation with antioxidants inhibited formation of thiobarbituric acid reactive substances to control levels; ethane evolution, when elevated, was also inhibited by antioxidants. The toxicity of diquat (100 micromolar-3 mM) was evaluated in liver slices; 1 and 3 mM diquat caused decreases in intracellular K+ and intracellular LDH. Preincubation with antioxidants substantially decreased the toxicity of diquat as indicated by K+ and LDH. Diquat significantly decreased total glutathione levels in the slices; the antioxidants did not significantly inhibit this diquat-dependent effect. In summary, diquat, a compound which undergoes redox cycling and produces oxidative stress, was shown to produce lipid peroxidation, glutathione depletion. and toxicity in liver slices. Two experimental antioxidants, a 21-aminosteroid (U-74,006F) and a trolox-amine (U-78,517G) as well as a known antioxidant (DPPD) were shown to be effective in preventing lipid peroxidation and reducing the subsequent toxicity |
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Bibliography: | H01 9324675 |
ISSN: | 0041-008X 1096-0333 |
DOI: | 10.1016/0041-008X(91)90121-T |