Antioxidants restore protoporphyrinogen oxidase in variegate porphyria patients.

BACKGROUND: Variegate porphyria (VP) is the result of decreased protoporphyrinogen oxidase (PPOX) activity and results in the accumulation of porphyrins and porphyrin precursors. Our aims were to analyse the basal antioxidant defences and oxidative damage markers and the effects of a diet supplementation with vitamins E and C on the oxidant/antioxidant status and PPOX gene expression in lymphocytes of variegate porphyria (VP) patients. MATERIALS AND METHODS: Twelve women affected by VP and 12 control women participated in a randomized and double-blind crossover study. Each participant took either 50 mg/day vitamin E and 150 mg/day vitamin C or a placebo for 6 months. RESULTS: Lymphocyte PPOX gene expression, together with catalase and glutathione peroxidase activities, was reduced in VP women. No differences were observed in the levels of malondialdehyde and protein carbonyl derivatives. Stimulated lymphocyte H2 O2 production was higher in porphyric women. Supplementation with antioxidant vitamins increased PPOX expression in VP patients. Glutathione reductase (GRd) and superoxide dismutase (SOD) activities were higher in the treatment groups. CONCLUSIONS: Lymphocytes from VP patients show reduced PPOX expression and present a greater susceptibility to producing H2 O2 and impaired H2 O2 detoxifying mechanisms. Supplementation with vitamins E and C restores PPOX expression in VP patients and enhances GRd and SOD activity, suggesting the potential benefits of a diet rich in vitamins E and C in these patients.

Variegate porphyria induces plasma and neutrophil oxidative stress: effects of dietary supplementation with vitamins E and C.

Our aim was to analyse the influence of variegate porphyria (VP) on the antioxidant defenses and markers of oxidative damage and inflammation in plasma and neutrophils and the effects of dietary supplementation with vitamins E and C on these parameters in plasma, neutrophils and erythrocytes. Twelve women affected by VP and twelve pair-matched healthy control women participated in a double-blind crossover study. Each participant took 50 mg/d of vitamin E and 150 mg/d of vitamin C, or a placebo, for 6 months, by consuming an almond-based beverage as the vehicle. Women affected by VP presented higher C-reactive protein and malondialdehyde (MDA) circulating levels. Plasma antioxidant defenses were not different between porphyric and control women. Neutrophils from VP women presented decreased catalase (CAT) and glutathione reductase (GR) activities together with increased protein carbonyl levels. Reactive oxygen species (ROS) production from stimulated neutrophils was also higher in porphyric women than their controls. Dietary supplementation was effective in increasing alpha-tocopherol levels in neutrophils and in reducing MDA levels in plasma. Erythrocyte CAT and GR activities were enhanced by the enriched beverage only in the control subjects. In conclusion, women affected by VP present a situation of inflammation, plasma oxidative damage and neutrophils more primed to the oxidative burst, with decreased antioxidant activities and increased ROS production capabilities and protein oxidative damage. Dietary supplementation with vitamin E (50 mg/d) and vitamin C (150 mg/d) for 6 months decreased plasma oxidative damage and enhanced the erythrocyte activities of CAT and GR.