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

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

Research output: Contribution to journalArticle

34 Citations (Scopus)

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
StatePublished - 1992

Fingerprint

Ruthenium Red
Hepatocytes
Oxidative Stress
Cell Death
tert-Butylhydroperoxide
Mitochondrial Membrane Potential
Proteolysis
Cell Survival
Wounds and Injuries
Calcium
Cytoprotection
Malondialdehyde
Mitochondria
Adenosine Triphosphate

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ruthenium red delays the onset of cell death during oxidative stress of rat hepatocytes. / Groskreutz, James L.; Bronk, Steven F.; Gores, Gregory James.

In: Gastroenterology, Vol. 102, No. 3, 1992, p. 1030-1038.

Research output: Contribution to journalArticle

Groskreutz, James L. ; Bronk, Steven F. ; Gores, Gregory James. / Ruthenium red delays the onset of cell death during oxidative stress of rat hepatocytes. In: Gastroenterology. 1992 ; Vol. 102, No. 3. pp. 1030-1038.
@article{860c78f467fb45ad86ea86ac67000b29,
title = "Ruthenium red delays the onset of cell death during oxidative stress of rat hepatocytes",
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.",
author = "Groskreutz, {James L.} and Bronk, {Steven F.} and Gores, {Gregory James}",
year = "1992",
language = "English (US)",
volume = "102",
pages = "1030--1038",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Ruthenium red delays the onset of cell death during oxidative stress of rat hepatocytes

AU - Groskreutz, James L.

AU - Bronk, Steven F.

AU - Gores, Gregory James

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026583939&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026583939&partnerID=8YFLogxK

M3 - Article

VL - 102

SP - 1030

EP - 1038

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -