Changes in microsomal phospholipases and arachidonic acid in experimental alcoholic liver injury: relationship to cytochrome P-450 2E1 induction and conjugated diene formation.
We evaluated the role of changes in microsomal phospholipases (A and C) and arachidonic acid in the intragastric rat feeding model. The experimental animals (male Wistar rats), divided into 4-5 rats/group, were fed the following diets: corn oil and ethanol and corn oil plus dextrose. One set of groups was killed after 2 weeks of feeding, and the second set was killed after 1 month. For each animal, microsomal analysis of cytochrome P-450 2E1 (CYP 2E1) and fatty acids was done. Fourteen animals had analyses of phospholipase C (PLC) and phospholipase A (PLA), and 10 animals had measurements of conjugated dienes. A significant correlation was obtained between the level of CYP 2E1 and the decrease in arachidonic acid (AA) from baseline levels (r = 0.69, p < 0.01). The decrease in AA also correlated with the increase in conjugated dienes (r = 0.70, p < 0.05). PLA and PLC activities were both significantly increased in the corn oil and ethanol groups. The activity of PLC correlated with the decline in AA (r = 0.69, p < 0.01). The correlations noted between the decrease in microsomal AA and CYP 2E1 induction and conjugated diene formation suggest that these processes may be interlinked especially in regard to generation of lipid peroxides that may play a role in alcoholic liver injury.
Nanji
A A
AA
Department of Pathology, New England Deaconess Hospital, Boston, MA 02215.
Zhao
S
S
Lamb
R G
RG
Sadrzadeh
S M
SM
Dannenberg
A J
AJ
Waxman
D J
DJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D010738:Type C Phospholipases / Q000378:metabolism
D005227:Fatty Acids; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D010740:Phospholipases; D010741:Phospholipases A; D010738:Type C Phospholipases