title: Effects of administration of antioxidants in acute intermittent porphyria.
abstract: In order to elucidate the question of free radical involvement in acute porphyric crisis, antioxidants were administered to two acute intermittent porphyria patients with long-standing recurrent attacks. Clinical condition and urinary excretion of porphyrins and porphyrin precursors were monitored before, during and after an eight week therapy with daily doses of vitamin E, beta-carotene, ascorbic acid, selenium, vitamin Q, acetylcysteine, mannitol and carnitine. Blood cell trace element profiles were followed. The administration of the compound antioxidant formula was found not to further impair the clinical or biochemical conditions of the patients but the incidence of the recurrent crises or the severity of the symptoms were not positively affected. Aberrant blood cell trace element profiles with increased granulocyte manganese were normalized during treatment, on cessation of the therapy again resuming the abnormal pretreatment patterns, which may suggest an origin in oxidative stress. No correlation was observed between the concentration of granulocyte manganese and the excretion of 5-aminolaevulinic acid. Indications for participation of this porphyrin precursor in a radical generating process leading to generalized mitochondrial superoxide dismutase induction, as conceivably signalled by increased intracellular manganese, were thus not obtained. The failure to note a clinical response to antioxidant therapy may be due to factors dependent upon dosage of, or interaction between, the antioxidant compounds given, or on restricted bioavailability of the antioxidants at critical anatomical sites, and does not per se invalidate the model of acute porphyria as a hyperoxidative condition.
authors.affiliation: Porphyria Centre Sweden, Stockholm. stig.thunell@porfyricentrum.pp.se
authors.forename: S
authors.initials: S
authors.lastname: Thunell
authors.forename: D
authors.initials: D
authors.lastname: Andersson
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: A
authors.initials: A
authors.lastname: Henrichson
authors.forename: Y
authors.initials: Y
authors.lastname: Floderus
authors.forename: U
authors.initials: U
authors.lastname: Lindh
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D008297:Male; D008345:Manganese / Q000097:blood; D018384:Oxidative Stress; D017118:Porphyria, Acute Intermittent / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D011166:Porphyrins / Q000652:urine; D014131:Trace Elements / Q000097:blood
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D011166:Porphyrins; D014131:Trace Elements; D008345:Manganese; D002118:Calcium