TY - JOUR
T1 - A new compound-specific pleiotropic effect of statins
T2 - Modification of plasma gamma-tocopherol levels
AU - Werba, José P.
AU - Cavalca, Viviana
AU - Veglia, Fabrizio
AU - Massironi, Paola
AU - De Franceschi, Michela
AU - Zingaro, Lorenzo
AU - Tremoli, Elena
PY - 2007/7
Y1 - 2007/7
N2 - Gamma tocopherol (γ-T) is a recognized peroxynitrite scavenger, reputedly metabolized via the cytochrome P450 3A4 (CYP3A4). In this study, we assessed whether equipotent LDL-lowering doses of statins with or without inhibitory activity on CYP3A4 differently affect γ-T metabolism. Patients with ATP III criteria for statin use (n = 35) were randomly allocated to treatment with simvastatin 20 mg/day or pravastatin 40 mg/day. Plasma lipids, α-tocopherol (α-T), γ-T as well as the urinary excretion of the γ-T metabolite 2,7,8-trimethyl-2-(2′carboxyethyl)-6-hydroxychroman (γ-CEHC), were determined at baseline and after 6 weeks of treatment. Pravastatin and simvastatin equally reduced LDL-C (-42.8 ± 2.9 and -42.1 ± 3.0%) and α-T levels (-17.5 ± 4.2 and -12.2 ± 4.1%), and increased the α-T/LDL-C ratios (51.4 ± 14.6 and 60.4 ± 15%). Conversely, pravastatin did not affect whereas simvastatin significantly augmented plasma γ-T levels (22 ± 7.9%, p = 0.009, between groups p = 0.0045). Moreover, the γ-T/LDL-C ratio increased significantly more with simvastatin than with pravastatin (124 ± 23 versus 61.3 ± 22.1%, p = 0.05 between groups). In addition, pravastatin but not simvastatin increased the urinary excretion of γ-CEHC (34.3 ± 17.3%, p = 0.056; between groups p = 0.046). In conclusion, simvastatin and pravastatin produced distinct effects on γ-T metabolism, presumably as a result of different statin-CYP interactions.
AB - Gamma tocopherol (γ-T) is a recognized peroxynitrite scavenger, reputedly metabolized via the cytochrome P450 3A4 (CYP3A4). In this study, we assessed whether equipotent LDL-lowering doses of statins with or without inhibitory activity on CYP3A4 differently affect γ-T metabolism. Patients with ATP III criteria for statin use (n = 35) were randomly allocated to treatment with simvastatin 20 mg/day or pravastatin 40 mg/day. Plasma lipids, α-tocopherol (α-T), γ-T as well as the urinary excretion of the γ-T metabolite 2,7,8-trimethyl-2-(2′carboxyethyl)-6-hydroxychroman (γ-CEHC), were determined at baseline and after 6 weeks of treatment. Pravastatin and simvastatin equally reduced LDL-C (-42.8 ± 2.9 and -42.1 ± 3.0%) and α-T levels (-17.5 ± 4.2 and -12.2 ± 4.1%), and increased the α-T/LDL-C ratios (51.4 ± 14.6 and 60.4 ± 15%). Conversely, pravastatin did not affect whereas simvastatin significantly augmented plasma γ-T levels (22 ± 7.9%, p = 0.009, between groups p = 0.0045). Moreover, the γ-T/LDL-C ratio increased significantly more with simvastatin than with pravastatin (124 ± 23 versus 61.3 ± 22.1%, p = 0.05 between groups). In addition, pravastatin but not simvastatin increased the urinary excretion of γ-CEHC (34.3 ± 17.3%, p = 0.056; between groups p = 0.046). In conclusion, simvastatin and pravastatin produced distinct effects on γ-T metabolism, presumably as a result of different statin-CYP interactions.
KW - Cytochrome P450
KW - Gamma-tocopherol
KW - Pleiotropic effect
KW - Statins
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U2 - 10.1016/j.atherosclerosis.2006.06.020
DO - 10.1016/j.atherosclerosis.2006.06.020
M3 - Article
C2 - 16860808
AN - SCOPUS:34248631076
VL - 193
SP - 229
EP - 233
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 1
ER -