ABSTRACT
Objective To observe the effect of Prodifen ( Skf525A) on rat thoracic aorta artery stenosis after bal-loon angioplasty and to discuss the relationship between endogenous Cytochrome P 450/epoxyeicosatrienoic acids (CYP2J2/EETs) system and artery stenosis after vascular injury .Methods Totally 24 Wistar rats were randomly divided into four groups assigned to the following treatments:sham group, I group ( treated by ballon angioplasty for 15 d).Using sham+Skf group (administrated with Skf525A), I+Skf group (administrated with Skf525A, then treated by ballon angioplasty for 15 d).Relative luminal area (RLA) and the intimal proliferation index (IPI) were observed by HE staining;The expression of Cytochrome P450 epoxygenase 2J3 (CYP2J3) mRNA was deter-mined by semi-quatative reverse transcription polymerase chain reaction ( RT-PCR ); the level of 11 ,12-EET was detected by high pressure liquid chromatography ( HPLC) .Results Compared with sham group , RLA significantly decreased , IPI significantly increased , CYP2 J3 mRNA expression and the content of 11 ,12-EET all significantly increased in I group ( P<0.01 ) .Compared with I group , Skf525 A treatment significantly decreased RLA , in-creased IPI, and decreased CYP2J3 mRNA expression and the content of 11,12-EET (P<0.01).Conclusions CYP2J3/EETs system can inhibit stenosis after vascular injury .
ABSTRACT
Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms (IC50 values, 3.2-33.7 muM). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.