ascorbic-acid and Porphyria-Cutanea-Tarda

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Susceptibility; Down-Regulation; Humans; Mice; Mice, Knockout; Mutation; Porphyria Cutanea Tarda; Uroporphyrinogen Decarboxylase

Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and experimental uroporphyria. Since previous studies have suggested a role for ascorbate (AA) in suppressing uroporphyria in AA-requiring rats (in the absence of excess iron), the present study investigated whether AA could suppress uroporphyria produced by excess hepatic iron. Hepatic URO accumulation was produced in AA-requiring Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered either sufficient AA (1000 ppm) in the drinking water to maintain near normal hepatic AA levels or a lower intake (75 ppm) that resulted in 70 % lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation in the absence of administered iron, but not when iron dextran (300-500 mg Fe/kg) was administered. This effect of iron was not due to hepatic AA depletion since hepatic AA content was not decreased. The effect of iron to prevent AA suppression of hepatic URO accumulation was not observed until a high hepatic iron threshold was exceeded. At both low and high AA intakes, hepatic malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold by high doses of iron dextran. MDA was considerably increased even at low iron dextran doses, but without any increase in URO accumulation. The level of hepatic CYP1A2 was unaffected by either AA intake.. In this mouse model of PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron levels. These results may have implications for the management of PCT.

Topics: Aminolevulinic Acid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 CYP1A2; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Iron; Iron-Dextran Complex; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Polychlorinated Biphenyls; Porphyria Cutanea Tarda; Uroporphyrins

50 Patients with chronic renal failure undergoing hemodialysis with or without porphyria cutanea tarda (PCT)-like skin changes were investigated. The total porphyrin amount in erythrocytes, plasma and dialysate and the distribution of porphyrin metabolites in plasma and dialysate were measured. In plasma, the group of patients with skin changes (referred as PCU = porphyria cutanea uremica) showed significantly increased uroporphyrin levels as compared to the non-symptomatic group. In addition, significant differences concerning the ratio uro-/coproporphyrin in plasma were shown: non-symptomatic patients with 0.87, as opposed to the PCU group with 3.7. Considerable differences between the level of vitamin ingestion were identified between the groups. Patients with PCU took distinctly less vitamins C, E and B than patients without symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Coproporphyrins; Dose-Response Relationship, Drug; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Porphyria Cutanea Tarda; Reference Values; Renal Dialysis; Risk Factors; Uremia; Uroporphyrins; Vitamin B Complex; Vitamin E; Vitamins

Porphyria cutanea tarda (PCT), the most common form of porphyria, is manifested as skin photosensitivity caused by excess hepatic production of uroporphyrin and heptacarboxylporphyrin. In experimental animal models, ascorbic acid modulates chemically induced uroporphyrin accumulation. The purpose of this study was to determine whether ascorbic acid is decreased in the plasma of patients with PCT. Plasma was obtained after an overnight fast from 21 PCT patients, 16 of whom were infected with hepatitis C virus (HCV), and from a separate group of 9 patients with HCV infection but not PCT. Thirteen PCT patients were studied when they had active disease and 8 after treatment-induced remission. Plasma ascorbic acid was low (<23 micromol/L) in 11 (85%) of the 13 untreated PCT patients and deficient (<11 micromol/L) in 8 (62%). Two patients with normal ascorbic acid levels (45 and 62 micrommol/L) had consumed multivitamins. In 2 patients with deficient ascorbic acid, plasma levels returned to normal after phlebotomy treatment. Of the 8 patients studied during remission, 4 had normal ascorbic acid values and 4 were deficient (5 to 8 micromol/L). Plasma ascorbic acid values were normal for all patients who had HCV but no PCT. These data suggest that plasma ascorbic acid concentrations are commonly low in PCT, but this decrease is unrelated to HCV infection. Ascorbic acid deficiency may be one of the factors that contributes to the pathogenesis of PCT.

Topics: Adult; Alanine Transaminase; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartate Aminotransferases; Female; Ferritins; Hepatitis C; Humans; Male; Middle Aged; Pilot Projects; Porphyria Cutanea Tarda; Transferrin