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Effect of Zinc on Hepatic Drug Metabolism under Ethanol Toxicity
- Source :
- Drug and Chemical Toxicology. 31:163-173
- Publication Year :
- 2008
- Publisher :
- Informa UK Limited, 2008.
-
Abstract
- The effects of zinc on drug-metabolizing enzymes in the liver were examined in male Wistar rats following ethanol intoxication. Rats were orally fed 3 mL of 30% ethanol daily for either two, four, or eight weeks and were orally administered zinc sulfate (ZnSO4.7H2O) at a dose level of 227 mg/L. Levels of reduced glutathione (GSH) and the activities of cytochrome P-450, cytochrome b(5), NADPH cytochrome-C-reductase and glutathione-S-transferase (GST) were determined in liver after two, four, and eight weeks. Significant elevation was observed in the activities of the enzymes of the mixed function oxidase system in response to toxicity induced by ethanol at all the intervals. These effects of were ascribed to the enhanced activity of the microsomal ethanol oxidizing system and the associated increase in reactive oxygen species production. Zinc supplementation to these ethanol-intoxicated animals resulted in normalization of these elevated values significantly, but still they do not attain normal levels. Significant increase was observed in reduced glutathione content in animals after four and eight weeks of ethanol feeding, which appeared to be further elevated in combined zinc and ethanol treatment. Significant elevation in the activity of GST was illustrated on ethanol-fed animals at all the three treatment intervals. Furthermore, the activity of this enzyme was only moderately normalized following zinc treatment. This was accredited to the antioxidant potential of zinc, as well as its ability to induce metallothionein content, which provide protection against the toxic effects of ethanol. To conclude, zinc was able to normalize the effects of ethanol in the liver.
- Subjects :
- Hemeproteins
Male
medicine.medical_specialty
Time Factors
Health, Toxicology and Mutagenesis
Administration, Oral
chemistry.chemical_element
Zinc
Toxicology
Antioxidants
Microsomal ethanol oxidizing system
Heme-Binding Proteins
chemistry.chemical_compound
Cytochrome P-450 Enzyme System
Internal medicine
medicine
Animals
Rats, Wistar
Glutathione Transferase
NADPH-Ferrihemoprotein Reductase
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
Chemical Health and Safety
Ethanol
Public Health, Environmental and Occupational Health
General Medicine
Glutathione
Metabolism
Zinc Sulfate
Rats
Oxidative Stress
Endocrinology
Liver
chemistry
Toxicity
Metallothionein
Carrier Proteins
Reactive Oxygen Species
Drug metabolism
Subjects
Details
- ISSN :
- 15256014 and 01480545
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Drug and Chemical Toxicology
- Accession number :
- edsair.doi.dedup.....6d3c74d014f3dc3516a76fecc94cb4f2