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The difference of glutathione antioxidant system in newly weaned and young mice liver and its involvement in isoline-induced hepatotoxicity
- Source :
- Archives of Toxicology. 85:1267-1279
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- Cellular glutathione antioxidant system plays important roles in counteracting hepatotoxins-induced oxidative stress injury. The present study was designed to observe the differences of this system in newly weaned and young mice liver and its involvement in the susceptibility to isoline-induced liver injury. Our results showed that liver reduced glutathione (GSH) amounts were higher in newly weaned mice than young mice. Glutamate-cysteine ligase (GCL) activity was higher in newly weaned mice due to the higher expression of catalytic subunit of GCL (GCLC) protein and mRNA. However, the activities of glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were higher in young mice liver, which might be due to the higher expression of GR, GPx-1, and GST-Pi proteins. Next, the results of AST analysis and histopathological evaluation showed that newly weaned mice demonstrated more severe liver injury induced by isoline. Furthermore, liver GSH amounts and the activities of GR, GPx, and GST were all lower in newly weaned mice than young mice after treated with isoline. Depletion of cellular GSH by D,L -buthionine-(S, R)-sulfoximine (BSO) aggravated isoline-induced cytotoxicity, while N-acetyl-l cysteine (NAC) ameliorated such cytotoxicity. Furthermore, the inhibitors of GR, GPx, and GST all aggravated isoline-induced cytotoxicity. In conclusion, our results demonstrated the differences of glutathione antioxidant system between newly weaned and young mice liver. Meanwhile, our results also revealed age-dependent liver injury induced by isoline for the first time, which might be due to the different responses of glutathione antioxidant system to isoline between newly weaned and young mice.
- Subjects :
- Male
medicine.medical_specialty
Antioxidant
Glutamate-Cysteine Ligase
Health, Toxicology and Mutagenesis
medicine.medical_treatment
Glutathione reductase
Weaning
Biology
Toxicology
medicine.disease_cause
Antioxidants
Mice
chemistry.chemical_compound
Internal medicine
medicine
Animals
Cytotoxicity
Pyrrolizidine Alkaloids
Glutathione Transferase
chemistry.chemical_classification
Liver injury
Glutathione Peroxidase
Mice, Inbred ICR
Glutathione Disulfide
Glutathione peroxidase
Age Factors
General Medicine
Glutathione
medicine.disease
Glutathione Reductase
Endocrinology
GCLC
Liver
Biochemistry
chemistry
Chemical and Drug Induced Liver Injury
Oxidative stress
Subjects
Details
- ISSN :
- 14320738 and 03405761
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Archives of Toxicology
- Accession number :
- edsair.doi.dedup.....52bfcc641a9c99f30b6982cd56750c63