Makhi SanfordMakhi Sanford
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We thus sought to analyze the effect of Atorvastatin antioxidant nutrients ( supplements vitamin Lipitor ) and gemfibrozil, as well as specific hydroxylated metabolites, on the susceptibility of LDL, very low density lipoprotein (VLDL), and high vitamin b vitamin e density lipoprotein (HDL) to oxidation. LDL oxidation induced by either copper antioxidant nutrients ions (10 microM CuSO4), by the free radical generator system 2'-2'-azobis 2-amidino propane hydrochloride (5 mM AAPH), or by antioxidants pills the diet vitamins J-774A.1 macrophage-like cell line, was not inhibited by the parent forms of Atorvastatin ( Lipitor ) or gemfibrozil, but antioxidants was substantially inhibited (57-97%), in a concentration-dependent manner, by pharmacological supplements for hair concentrations of the o-hydroxy and the p-hydroxy metabolites of Atorvastatin ( Lipitor ), as well as by the p-hydroxy metabolite (metabolite I) nutritional supplements of gemfibrozil. Similar inhibitory effects (37-96%) of the above metabolites were obtained for the susceptibility of VLDL and HDL to oxidation in the oxidation systems outlined above. In addition, inhibition of HDL oxidation was associated with the preservation diet vitamins of HDL-associated paraoxonase activity. Although this antioxidative effect could not be obtained in vitro with all of these drugs, the active drug metabolites, which are formed in vivo, could affect lipoprotein oxidizability. antioxidants We hypothesize that in addition to their beneficial lipid regulating activity, specific metabolites of both drugs may also reduce the atherogenic potential of lipoproteins through their antioxidant properties.. On using the Atorvastatin ( Lipitor ) o-hydroxy metabolite and gemfibrozil metabolite I in combination an additive inhibitory effect on LDL oxidizability was found. The inhibitory effects of these metabolites on LDL, VLDL, and HDL oxidation could be related to their free radical scavenging activity, as well as (mainly for the gemfibrozil metabolite I) to their metal ion chelation capacities. Atorvastatin ( Lipitor ) and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein creased atherosclerosis risk in hyperlipidemic patients may be a result of the enhanced oxidizability of their plasma lipoproteins. We conclude that Atorvastatin ( Lipitor ) hydroxy metabolites, and gemfibrozil metabolite I possess potent antioxidative potential, and as a result protect LDL, VLDL, and HDL from oxidation. We have previously shown that hypocholesterolemic drug therapy, including the 3-hydroxy-3-methyl-glutaryl CoenzymeA (HMG-CoA) reductase inhibitors, and the hypotriglyceridemic drug bezafibrate, significantly reduced the enhanced susceptibility to oxidation of low density lipoprotein (LDL) isolated from hyperlipidemic patients.
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