RGD Reference Report - Attenuation of endogenous oxidative stress-induced cell death by cytochrome P450 inhibitors in primary cultures of rat hepatocytes. - Rat Genome Database

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Attenuation of endogenous oxidative stress-induced cell death by cytochrome P450 inhibitors in primary cultures of rat hepatocytes.

Authors: Shiba, D  Shimamoto, N 
Citation: Shiba D and Shimamoto N, Free Radic Biol Med. 1999 Nov;27(9-10):1019-26.
RGD ID: 5130878
Pubmed: PMID:10569634   (View Abstract at PubMed)

This study reports an examination of the effects of endogenous oxidative stress on primary cultures of rat hepatocytes. To produce endogenous oxidative stress, 3-amino-1,2,4-triazole (ATZ) and mercaptosuccinic acid (MS), which are known to inhibit catalase and glutathione peroxidase activities, respectively, were used. When ATZ or MS was used alone, the extent of cell injuries was negligible, but a combination of the two agents resulted in cell death as assessed by trypan blue exclusion after 24 h of incubation. Cell death was accompanied by an approximately 5.8-fold the increase in the levels of thiobarbituric acid reactive substances, and showed chromatin condensation and DNA fragmentation. These deleterious effects were time dependent in that no significant change was detected up to 6 h. Treatment with SKF or 1-aminobenzotriazole, which are inhibitors of cytochrome P450, greatly attenuated this cell death as well as prevented chromatin condensation and DNA fragmentation. N(G)-monomethyl-L-arginine at 1 mM had no inhibitory effects on these changes. These findings suggest that endogenous oxidative stress under these conditions induced cell death that resembles apoptosis and that endogenous oxidative stress was directly related to the cytochrome P450 enzyme system in this system.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
stomatitis  ISOCat (Rattus norvegicus)5130878; 5130878 RGD 
stomatitis  IEP 5130878 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IMP 5130878 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cat  (catalase)

Genes (Mus musculus)
Cat  (catalase)

Genes (Homo sapiens)
CAT  (catalase)


Additional Information