Elevated plasma homocysteine elicits an increase in antioxidant enzyme activity

Elevated plasma homocysteine is considered to be a risk factor for cardiova scular disease. The mechanisms for this effect are not fully understood but there is some evidence for a role for reactive oxygen species (ROS). This study was conducted to explore the effects of elevated plasma total homocys teine (tHcy) concentration on activity of antioxidant enzymes in the circul ation. The study group consisted of 10 patients with inherited defects of h omocysteine metabolism, from whom 41 blood samples were collected over a pe riod of six months. Blood samples were also collected from 13 of their obli gate heterozygous parents. For data analysis samples were classified as tho se with plasma tHcy < 20 mu M or greater than or equal to 20 mu M. The acti vity of erythrocyte superoxide dismutase (SOD) and plasma glutathione per o xidase (GSHPx) was elevated in samples with plasma tHcy > 20 mu M. Moreover , a significant correlation was demonstrated between plasma GSHPx activity, plasma glutathione peroxidase protein and plasma tHcy. In vitro studies co nfirmed that this observation was not due to a simple chemical enhancement of enzyme activity. Homocysteine protected GSHPx from loss of activity foll owing incubation at 37 degrees C. A similar effect was seen with another th iol-containing amino acid, cysteine. Results suggest that elevated plasma t Hcy represents an oxidative stress, resulting in an adaptive increase in ac tivity of antioxidant enzymes in the circulation.