Impaired lymphocyte mitochondrial antioxidant defences in variegate porphyria are accompanied by more inducible reactive oxygen species production and DNA damage.

This study aimed to analyse lymphocyte reactive oxygen species (ROS) production and detoxification mechanisms and the appearance of oxidative damage in variegate porphyria (VP) patients. Twelve women affected by VP and 12 pair-matched healthy control women participated in the study. VP women presented impaired expression of the mitochondrial proteins protoporphyrinogen oxidase, uncoupling protein-3, Bcl-2 and sirtuin 3. Lymphocytes from VP women presented higher H(2)O(2) production than controls after stimulation with phorbol myristate acetate. The inhibition of H(2)O(2) production after in vitro lymphocyte treatment with myxothiazol pointed towards complex III of the mitochondrial respiratory chain as the main contributor of the higher ROS production in porphyric subjects. No differences were observed between VP and control subjects in the levels of DNA damage, assessed by the comet assay method in un-treated lymphocytes. However, DNA damage, expressed both as a percentage of DNA in tail and as the tail moment, was greater in VP women than controls after lymphocyte treatment with H(2)O(2). In conclusion, lymphocytes from VP women showed impaired expression of mitochondrial antioxidant defences but no significant signs of oxidative stress were evidenced in basal, non-stressing conditions; however, lymphocytes of VP women were more susceptible to producing mitochondrial ROS and to suffering oxidative damage when submitted to stressful situations.