Renal cytochrome P-450-dependent metabolism of arachidonic acid in cirrhotic rats.
Cirrhosis was induced in Wistar-Kyoto rats by intragastric administration of carbon tetrachloride. Microsomes were obtained from the renal cortex and outer medulla and incubated with [14C]arachidonic acid (AA) (0.2-0.4 microCi) in the presence or absence of indomethacin, NADPH, and SKF-525A. Cytochrome P-450-dependent AA metabolites (those whose formation required NADPH, were inhibited by SKF-525A, but not by indomethacin) were separated by thin-layer chromatography and high-pressure liquid chromatography (HPLC). Compared to controls, total synthesis of cytochrome P-450-dependent AA metabolites was reduced in cirrhotic rats (renal cortex: cirrhotics 380 +/- 52 vs. controls 493 +/- 68 pg/mg protein per 30 min; p less than 0.05; renal outer medulla: cirrhotics 304 +/- 57 vs. controls 387 +/- 53 pg/mg protein per 30 min; p less than 0.05). The cytochrome P-450-dependent AA metabolites were composed of three peaks separated by HPLC. Peak I, which had a retention time of 16.3 +/- 0.3 min and comigrated with 11,12-dihydroxyeicosatrienoic acid, and peak II, which had a retention time of 18.7 +/- 0.4 min and comigrated with 19- and 20-hydroxyeicosatetraenoic acid, were not different in cirrhotics and controls. Peak III, which had a retention time of 26.8 +/- 0.3 min, and comigrated with 11,12-epoxyeicosatrienoic acid, was significantly decreased in the renal cortex of cirrhotic rats compared to controls (cirrhotics 316 +/- 40 vs. controls 473 +/- 89 pg/mg protein per 30 min; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Sacerdoti
D
D
Department of Pharmacology, New York Medical College, Valhalla, NY.
Escalante
B A
BA
Schwartzman
M L
ML
Abraham
N G
NG
Gatta
A
A
McGiff
J C
JC
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases