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The CYP inhibitor 1-aminobenzotriazole does not prevent oxidative stress associated with alcohol-induced liver injury in rats and mice
- Source :
- Free Radical Biology and Medicine. 35:1568-1581
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Cytochrome P450 (CYP) 2E1 is induced by ethanol and is postulated to be a source of reactive oxygen species during alcoholic liver disease. However, there was no difference in liver pathology and radical formation between wild-type and CYP2E1 knockout mice fed ethanol. Other CYP isoforms may contribute these effects if CYP2E1 is inhibited or absent. The purpose of this study was, therefore, to determine if blocking most of the P450 isoforms with 1-aminobenzotriazole (ABT; 100 mg/kg i.g.), has any effect on liver damage and oxidative stress due to alcohol in rats and mice. Male C57BL/6 mice and Wistar rats were fed either high-fat control or ethanol-containing enteral diet for 4 weeks. ABT had a significant inhibitory effect on many P450 isoforms independent of concomitant alcohol administration. However, ABT did not protect against liver damage due to alcohol in either species. Indices of oxidative stress and inflammation were also similar in livers from vehicle-treated and ABT-treated animals fed ethanol. In summary, suppression of P450 activity with ABT had no apparent effect on oxidative stress caused by alcohol in both rats and mice. These data support the hypothesis that oxidative stress and liver damage can occur independently of CYP activities in both rats and mice during early alcohol-induced liver injury.
- Subjects :
- Male
medicine.medical_specialty
Alcoholic liver disease
medicine.disease_cause
Biochemistry
4-Hydroxynonenal
Mice
Liver disease
chemistry.chemical_compound
Physiology (medical)
Internal medicine
medicine
Animals
RNA, Messenger
Enzyme Inhibitors
Rats, Wistar
Mice, Knockout
chemistry.chemical_classification
Liver injury
Reactive oxygen species
Ethanol
Electron Spin Resonance Spectroscopy
Alanine Transaminase
Cytochrome P-450 CYP2E1
Triazoles
CYP2E1
medicine.disease
Immunohistochemistry
Rats
Cytochrome P-450 CYP2E1 Inhibitors
Mice, Inbred C57BL
Oxidative Stress
Endocrinology
chemistry
Enzyme Induction
Chemical and Drug Induced Liver Injury
Oxidative stress
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....abb451ee9c91e5161f029acb9697e2ca
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2003.09.007