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Changes in cytochromes P-450, 2E1, 2B1, and 4A, and phospholipases A and C in the intragastric feeding rat model for alcoholic liver disease: relationship to dietary fats and pathologic liver injury
- Source :
- Alcoholism, clinical and experimental research. 18(4)
- Publication Year :
- 1994
-
Abstract
- The influence of dietary fat and alcohol on hepatic microsomal levels of cytochromes P-450 2E1, 2B, and 4A; phospholipases A and C; and UDP-glucuronosyltransferase was studied in the intragastric feeding rat model for alcoholic liver injury. Eight groups of animals were evaluated. Control and ethanol fed rats received either saturated fat or corn oil and were killed after 2 weeks and 1 month of feeding. All animals were pair-fed by continuous infusion of liquid diet through permanently implanted gastric cannulas. Alcoholic liver injury developed only in the corn oil-ethanol-fed groups and was manifest by 1 month. Livers were subjected to the following analyses: pathologic evaluation of liver injury; levels of cytochromes P-450 2E1, 2B, and 4A protein and mRNA; aniline hydroxylase activity; and phospholipase A and C and UDP-glucuronosyltransferase activities. Ethanol-induced increases in cytochromes P-450 2E1 and 2B protein determined by Western blotting were greatest in the corn oil-ethanol-fed group, which developed pathologic changes in the liver. Cytochromes P-450 2E1 and 2B1 mRNA levels were unaffected, suggesting that posttranscriptional mechanisms are responsible for the increase in the corresponding P-450 proteins. In contrast, cytochrome P-450 4A levels were higher in the saturated fat-ethanol groups compared with the corn oil-ethanol groups. Phospholipase A and phospholipase C levels were higher in the corn oil-ethanol groups compared with pair-fed dextrose controls and the saturated fat-ethanol groups. UDP-glucuronosyltransferase levels declined with time in the ethanol-fed groups. These observations are discussed in the context of a model whereby the induction of phospholipases A and C and cytochromes P-450 2E1 and 2B1 in corn oil-ethanol-fed rats provide arachidonic acid substrate and induce lipid peroxidation, respectively. These changes may account for the more severe pathologic changes that develop in corn oil-ethanol-fed animals compared with animals fed saturated fat and ethanol.
- Subjects :
- Male
Alcoholic liver disease
medicine.medical_specialty
Liquid diet
Saturated fat
Medicine (miscellaneous)
Biology
Toxicology
Phospholipases A
Mixed Function Oxygenases
chemistry.chemical_compound
Phospholipase A1
Cytochrome P-450 Enzyme System
Liver Cirrhosis, Alcoholic
Internal medicine
medicine
Animals
Glucuronosyltransferase
Rats, Wistar
Liver injury
Phospholipase A
Cytochrome P-450 CYP2E1
Oxidoreductases, N-Demethylating
medicine.disease
Dietary Fats
Rats
Psychiatry and Mental health
Endocrinology
chemistry
Liver
Type C Phospholipases
Arachidonic acid
Corn Oil
Corn oil
Subjects
Details
- ISSN :
- 01456008
- Volume :
- 18
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Alcoholism, clinical and experimental research
- Accession number :
- edsair.doi.dedup.....c950ea2465865cc8f6bfcd5c209dd39e