Increase of protein and lipid oxidation during hyperhomocysteinemia induced by methionine oral loading

Introduction: Hyperhomocysteinemia (HHcy) is a well-defined risk factor for vascular disease by a not still well clear molecular mechanism. It is known a pro-oxidant effect of Hcy “in vitro” in presence of metal ions (Fe e Cu). To assay a similar effect in vivo, we studied plasma markers of lipid and protein oxidation during hyperhomocysteinemia induced by methionine oral load.Materials and methods: 16 subjects (aged 79  14 years; 16f), 14 of which underwent a methionine (100 mg/Kg) oral load were studied; in all patients we assayed total plasma HCY, malonaldehyde (MDA) and conjugates dienes (DIE), oxidized protein (PTOX) (carbonilic groups) in basal conditions and after 4, 6, 8 and 24 hours from the oral load. In the two subjects who did not take the methionine load (controls), were made the same assays with the same timing of the probands. In all subjects we assayed basal and after 8 hours from the methionine load total plasma antioxidant (ANTOX) capacity.Results: table shows values (mean  DS) of considered parameters in subjects who underwent the methionine loadParameterBasal4 h6 h8 h24 hHcy (nmol/ml)20.7  11.550.6  19.157.2  25.561.6  28.3 45.3  30.7PTOX (nmol/mg prot.)0.38  0.210.49  0.270.68  0.390.68  0.270.58  0.40DIE(nmol/ml)493  163562  181526  233590  202545  182MDA(nmol/ml)1.66  0.801.91  0.942.19  1.321.96  0.931.95  0.99ANTOX(nmol/ml)1.76 +/- 0.511.38 +/- 0.86 Conclusions: HHCY induces a correspondent increase of plasma oxidation makers. In absence of HHCY, no significant modifications were observed. This data, together with the reduction of ANTOX in correspondence of maximum plasma HCY increase, are suggestive of pro-oxidant effect of HHCY in vivo.