Toxicity of t-Butylhydroperoxide in Hepatocyte Monolayers Exposed to Hypoxia and Reoxygenation

Inasmuch as it is known that the toxicity of anesthetic agents is potentiated by hypoxia and that the reductive metabolism of these agents results in the formation of lipid hydroperoxides, we investigated the toxicity of hydroperoxides under low-oxygen concentrations. We found that hypoxia exacerbat...

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Bibliographic Details
Published in:In vitro cellular & developmental biology 1987-07, Vol.23 (7), p.501-506
Main Authors: Costa, Anita K., Dominic F. Heffel, Thomas M. Schieble, Trudell, James R.
Format: Article
Language:English
Subjects:
Animals
Aspartate Aminotransferases - metabolism
Biological and medical sciences
Cell Survival - drug effects
Cells, Cultured
Cellular metabolism
Chemical hazards
Cytochromes
Drug toxicity and drugs side effects treatment
Free radicals
Hepatocytes
Hypoxia
Incubators
Kinetics
Lipid metabolism
Liver
Liver - drug effects
Liver - pathology
Male
Medical sciences
Oxygen
Peroxides - toxicity
Pharmacology. Drug treatments
Rats
Rats, Inbred Strains
tert-Butylhydroperoxide
Toxicity: digestive system
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Summary:Inasmuch as it is known that the toxicity of anesthetic agents is potentiated by hypoxia and that the reductive metabolism of these agents results in the formation of lipid hydroperoxides, we investigated the toxicity of hydroperoxides under low-oxygen concentrations. We found that hypoxia exacerbates the toxicity of t-butyl hydroperoxide, shifting the dose-response curve of t-butyl hydroperoxide vs. lysis of hepatocytes approximately an order of magnitude to the left. Furthermore, although at the end of a 4-h exposure to$0.5\% O_2$hepatocyte monolayers seemed normal by three indices (release of51Cr and serum glutamate transaminase or exclusion of trypan blue), they were completely lysed after an additional 20 h reoxygenation at$20\% O_2$. In contrast, monolayers exposed to$2\% O_2$for 4 h seemed normal after 20 h reoxygenation. However, cells exposed to both a subtoxic dose of hydroperoxide and 4 h of$2\% O_2$, although seeming healthy at the end of the hypoxic period, were completely lysed within 20 h after reoxygenation.
ISSN:0883-8364
2327-431X
DOI:10.1007/BF02628420