Effect of carrageenan-induced granuloma on hepatic cytochrome P-450 isozymes in rats.
Carrageenan-induced granuloma was used to study the apoprotein and RNA content, and catalytic activities of several cytochrome P-450 isozymes in liver. This model allowed discrimination between acute and chronic phases of experimental inflammation. The expression of most isozymes studied (CYP2D, CYP2E1, CYP3A1 and CYP4A) was reduced to 20% of the control level during the acute phase and partially recovered (30-60% of control group) during the chronic phase. CYP2B1 content was decreased to 65% of control during the acute and chronic phases of inflammation. RNA (CYP2B1 and CYP2E1) showed a strong depression during the acute phase and recovered during the chronic phase, without differences between isoenzymes. In most cases, there was a good correlation between the apoprotein content of isozymes and related activities. Our results show that the depletion of cytochrome P-450 induced by inflammation depends on the severity of the disease. Experimental inflammation equally affect the transcription of CYP2B1 and CYP2E1, so differences in apoprotein content and related activities between isozymes may due to differential posttranscriptional regulation.
Muntané
J
J
Laboratory of Genetics and Biochemical Toxicology, Instituto di Mutagenesi e Differenziamento, CNR, Pisa, Italy.
Longo
V
V
Mitjavila
M T
MT
Gervasi
P G
PG
Ingelman-Sundberg
M
M
D000208:Acute Disease; D000818:Animals; D001051:Apoenzymes / Q000032:analysis*; D002351:Carrageenan / Q000633:toxicity*; D002908:Chronic Disease; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004790:Enzyme Induction / Q000187:drug effects; D006099:Granuloma / Q000139:chemically induced / Q000201:enzymology*; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012871:Skin Diseases / Q000139:chemically induced / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism
D001051:Apoenzymes; D007527:Isoenzymes; D012333:RNA, Messenger; D013739:Testosterone; D002351:Carrageenan; D003577:Cytochrome P-450 Enzyme System