Evidence for free radical-mediated reduction of lymphocytic 5′-ectonucleotidase during stress

Previously we showed that stress and depression could result in a 50% lowering of lymphocytic 5'-ectonucleotidase (NT) which could be resolved by a diet high in antioxidants. This study suggested that high levels of free radicals mediated by stress/depression may be involved in lowering NT activities. The aim of the present study was to assess whether oxygen radicals could directly affect NT and whether excess free radicals generated in stress/depression may affect tissue ascorbate stores. Exam-stressed students and depressed patients were compared respectively to these students at low stress and depressed patients on high antioxidant intakes. In this study, NT correlated positively with tissue ascorbate stores. A range of antioxidants were tested as possible inhibitors of oxy radical interaction with NT using nitroblue tetrazolium reduction to formazan with superoxide anion. At physiological plasma concentrations ascorbate inhibited this reduction but dehydroascorbate, tocopherol, retinol, selenium, urate, and reduced glutathione were ineffective. Superoxide anion directly reduced lymphocytic NT activity and this effect was reversed by either 100 mu molar ascorbate in vitro or a high antioxidant intake in vivo. In conclusion, the low NT activities and ascorbate stores found in stressed/depressed people appear to be mediated by higher levels of free radicals reported in these subjects. These conclusions are consistent with published reports of (1) normal NT levels in melancholic patients on high antioxidant diets; (2) heightened inflammatory reponses during stress/depression; (3) low serum levels of zinc in depressed patients.