Blood glutathione detects pro-oxidant patterns in mild hyperhomocysteinemia associated with atherothrombotic vascular events

Abstract number: P0442

Parodi^* O., Baudo† F., Devoto† E., De Maria§ R., De Chiara§ B., Campolo§ J., Caruso§ R., Brunelli† C., Accinni§ R.

^*CNR Clinical Physiology Institute, Italy; §CNR Clinical Physiology, Italy †Department of Internal Medicine, Italy; †Thrombosis Hemostasis, Italy;

Background  

Hyperhomocysteinemia limits the bioavailability of nitric oxide by a mechanism involving glutathione (GSH) peroxidase. An anti-oxidant/pro-oxidant imbalance induced by transient hyperhomocysteinemia may uncover abnormal GSH bioavailability favoring vascular damage.

Methods and results  

We examined the effect of hyperhomocysteinemia 4 h postmethionine loading (PML) on plasma thiols, anti-oxidant vitamins, free malondialdehyde, and blood reduced GSH in 44 patients with hyperhomocysteinemia and 12 age- and sex-matched healthy subjects with normal homocysteine levels. Sixteen patients had had previous atherothrombotic vascular events. Percent changes in blood GSH 4 h PML best discriminated hyperhomocysteinemic from control subjects by multivariate linear regression analysis with a 58% cut-off value. This delta GSH cut-off was used to classify hyperhomocysteinemic patients in Group 1 (<=58%, n = 31) or Group 2 (>58%, n = 13). Prevalence of vascular events was higher in Group 1 (48%) than in Group 2 (8%, P = 0.02), OR 11 (95% CI: 1.3–97). Despite comparable baseline and PML homocysteine levels, Group 1 had significantly higher baseline levels of blood GSH (439 ± 265 mmol L^-1) than Group 2 (295 ± 133 mmol L^-1) and controls (250 ± 92 mmol L^-1, P = 0.02). Delta blood GSH also predicted different metabolic patterns PML: in Group 1 plasma reduced forms of cysteine, GSH and cysteinylglycine were significantly higher than in Group 2 and controls, and vitamin E declined significantly; conversely, vitamin E was stable in Group 2 and controls.

Conclusions  

In hyperhomocysteinemia, high baseline GSH content in blood, and its inability to increase PML, identify a pro-oxidant metabolic pattern associated with atherothrombotic vascular events.