Ruthenium red delays the onset of cell death during oxidative stress of rat hepatocytes

James L. Groskreutz, Steven F. Bronk, Gregory J. Gores

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Abstract

Our objective was to determine if ruthenium red protects against lethal oxidative injury of rat hepatocytes. tert-Butyl hydroperoxide, 100 μmol/L, was used to produce oxidative stress. After 2 hours of oxidative stress, cell viability was greater with than without 25 μmol/L ruthenium red (37% vs. 4.6%; P < 0.01). Despite this cytoprotection, ruthenium red did not alter the rate or extent of glutathi one depletion, malondialdehyde generation, or adenosine triphosphate depletion. In contrast, ruthenium red did retard loss of the mitochondrial membrane potential (78% vs. 42% within 30 minutes; P < 0.01). However, the protective effect of ruthenium red could not solely be explained by preserving the mitochondrial membrane potential. Indeed, ruthenium red still improved cell survival after 2 hours of exposure to 10 μmol/L carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler (39% vs. 13%; P < 0.01). Cytosolic free calcium values did not change during the uncoupling of mitochondria, suggesting that the cytoprotective properties of ruthenium red cannot be explained by blocking mitochondrial calcium transport. Ruthenium red did inhibit proteolysis after 2 hours of exposure to tert-butyl hydroperoxide (434 ± 62 vs. 242 ± 20 nmol/106 cells; P = 0.016) or CCCP (236 ± 50 vs. 99 ± 38 nmol/106 cells; P = 0.04). The results indicate that ruthenium red appears to protect against hepatocellular injury by inhibiting degradative proteolytic activity. It is concluded that proteolysis may be an important mechanism contributing to lethal oxidative injury of hepatocytes.

Original languageEnglish (US)
Pages (from-to)1030-1038
Number of pages9
JournalGastroenterology
Volume102
Issue number3
DOIs
StatePublished - Mar 1992

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ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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