Changes in gene expression of cytochrome P-450 in liver, kidney and aorta of cirrhotic rats.
BACKGROUND
Liver cirrhosis is characterized by structural and hemodynamic changes that affect mainly the liver, the kidney and the vascular system. Cytochrome P-450 (CYP) is a variegated family of enzymes that, among many other activities, metabolize arachidonic acid to the vasoactive epoxyeicosatrienoic acids (EETs).


OBJECTIVE
To investigate in an animal model of cirrhosis the m-RNA expression of CYPs in liver, kidney and aorta and to evaluate the effect of epoxygenase inhibition by N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH).


METHODS
In aorta, liver and kidney from 3 control, 3 cirrhotic and 6 cirrhotic rats treated with MS-PPOH, quantitative real-time PCR reactions were performed and the m-RNA expression of CYP2J3, CYP2J4, CYP2J10, CYP2C11, CYP2C12 and CYP2C23 was calculated.


RESULTS
In cirrhotic rats, the gene expression of hepatic CYP2C11 and CYP2J10 was increased, of aortic CYP2J4 was increased, of aortic CYP2C12 was reduced and of renal CYP2C11 was increased. In cirrhotic rats, MS-PPOH reduced CYP2J10 hepatic and CYP2C11 renal gene expression to levels similar to the ones of control rats.


CONCLUSIONS
Changes in CYPs gene expression may contribute to the hemodynamic alterations typical of cirrhosis. The altered gene expression of CYPs can, in some cases, be reversed by epoxygenase inhibition.
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy. Electronic address: m.dipascoli@tin.it.
Marco
M
Di Pascoli
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Cristian
C
Turato
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Francesca
F
Zampieri
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Alberto
A
Verardo
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Patrizia
P
Pontisso
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Paola
P
Pesce
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
David
D
Sacerdoti
Department of Medicine-DIMED, University of Padua, Azienda Ospedaliera Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Massimo
M
Bolognesi
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; C000717351:Cyp2c23 protein, rat; C121756:N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2
Cytochrome P-450; Epoxyeicosatrienoic acids; Liver cirrhosis; Portal hypertension