Abstract
We hypothesized that M1, a metabolite of gemfibrozil, may have antioxidant properties because of its hydroxylated phenol ring, 5-(4-hydroxy-2,5-dimethyl-phenoxy)-2,2-dimethyl pentanoic acid. The susceptibility of low-density lipoprotein (LDL) to oxidative modification was investigated by a method using 2,2-azobis(4-methoxy-2,4-dimethylvaleronitrile [MeO-AMVN]) or Cu2+ as previously reported. Conjugated dienes (CDs), lipid hydroperoxide (LPO), and thiobarbituric acid-reactive substances (TBARS) were measured to evaluate the degree of LDL oxidation. Oxidized LDL (OxLDL), which is used for cytotoxicity studies, was prepared by the dialysis method using Cu2+ as the oxidation inducer. Cytotoxicity induced by OxLDL was studied in J774 macrophages by colorimetric assay using 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT assay). The oxidative modification of LDL was inhibited by M1 in a dose-dependent manner. The antioxidant effect of M1 on LDL oxidation was diminished by dialysis of the LDL incubated with M1 against phosphate-buffered saline (PBS), suggesting that M1 is hydrophilic rather than lipophilic. M1 diminished the cytotoxicity induced by OxLDL, although it was milder versus probucol. These data suggest that this gemfibrozil metabolite has an antioxidant effect on LDL, and thus M1 may contribute to the antiatherogenic effects of gemfibrozil.
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.
