Abstract
Cytochrome P450 1B1 (CYP1B1) has been reported to have a major role in metabolizing arachidonic acid (AA) into cardiotoxic metabolites, mid-chain hydroxyeicosatetraenoic acids (HETEs). Recently, we have shown that fluconazole decreases the level of mid-chain HETEs in human liver microsomes. Therefore, the objectives of this study were to investigate the effect of fluconazole on CYP1B1 mediated mid-chain HETEs and to explore its potential protective effect against angiotensin II- (Ang II)-induced cellular hypertrophy. To do this, Sprague Dawley rats were injected intraperitoneally with a single dose of fluconazole (20 mg/kg) for 24 h. Also, H9c2 and RL-14 cells were treated with 10 μM Ang II in the presence and absence of 50 μM fluconazole for 24 h. Our results demonstrated that treatment of rats with fluconazole significantly decreased the expression of CYP1B1 enzyme and the level of mid-chain HETEs in the heart. Furthermore, fluconazole was able to attenuate Ang–II–induced cellular hypertrophy as evidenced by a significant down-regulation of hypertrophic markers; β-myosin heavy chain (MHC)/α-MHC and brain natriuretic peptide (BNP) as well as cell surface area. In conclusion, our findings indicate that fluconazole protects against Ang II-induced cellular hypertrophy by repressing CYP1B1 and its associated mid-chain HETEs.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
