Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading

Hyperhomocysteinemia is a risk factor for vascular disease, although its me chanism of action is not fully clear. Different experimental studies have s uggested that homocysteine (Hcy) exerts a pro-oxidant effect in the presenc e of metal ions (Fe and Cu). To test for a similar effect in vivo, we studi ed plasma markers of lipid and protein oxidation du ring hyperhomocysteifie mia induced by an oral methionine load. Twenty-nine subjects (aged 61 +/- 2 5 years; 17 women), 25 of whom underwent oral methionine (100 mg/kg) loadin g, were studied; in every case, we measured total plasma Hey, malondialdehy de (MDA), conjugated dienes (DIE), and oxidized protein ([PTOX] carbonylic groups) in basal conditions and 4, 6, 8, and 24 hours after methionine load ing. Four participants acted as controls. In every case, we also measured t otal plasma antioxidant capacity (ANTOX) in basal conditions and 8 hours af ter methionine loading. Eight hours after methionine loading, plasma Hey in creased from 17.6 +/- 11.4 to 54.3 +/- 31.6 nmol/ml, PTOX from 0.33 +/- 0.1 8 to 0.71 +/- 0.33 nmol/mg protein, DIE from 493 +/- 163 to 590 +/- 202 opt ical density units, and MDA from 1.66 +/- 0.81 to 2.1 +/- 0.93 nmol/ml. The re was a significant correlation (Spearman's r) between Hey and both PTOX ( r = .86, P = .01) and MDA (r = .47, P < .05) 8 hours after methionine loadi ng. No significant modifications of the plasma parameters were found during the observation period in controls. ANTOX at 8 hours was significantly (pa ired ttest) reduced in probands (from 1.74 +/- 0.59 to 1.14 +/- 0.55 mmol/m l, P = .014); no significant difference was observed for plasma ANTOX in co ntrols. Hyperhomocysteinemia due to oral methionine loading induced an incr ease in plasma oxidation markers. In the absence of hyperhomocysteinemia. n o significant modifications were observed. These findings, together with th e decrease in ANTOX and the corresponding increase in total plasma Hey, are consistent with a pro-oxidant effect of acute hyperhomocysteinemia in vivo . Copyright (C) 2000 by W.B. Saunders Company.