ascorbic-acid and Porphyrias

Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.

Topics: Ascorbic Acid; Carcinoma, Hepatocellular; Collagen; Free Radicals; Hemochromatosis; Humans; Iron; Liver; Liver Cirrhosis; Liver Neoplasms; Lysosomes; Membrane Potentials; Porphyrias; Potassium; Transferrin; Uroporphyrins; Vitamin E

Topics: Abnormalities, Drug-Induced; Animals; Ascorbic Acid; Child; Chloroquine; Enzymes; Eye Diseases; Female; Humans; Lysosomes; Pigmentation; Porphyrias; Pregnancy; Protein Biosynthesis; Psoriasis; Pyridoxine; Rabbits; Retina; Ultraviolet Rays

Sublethal doses of cadmium chloride (2.5, 5.0 and 10.0 mu mole/kg egg weight) were found to significantly alter the first two rate limiting enzymes of heme biosynthesis in chick embryos. Delta-aminolevulinic acid synthase activity was elevated by 2.05 and 2.11 fold with 5.0 and 10.0 mu moles of cadmium treatment respectively. However, this was reduced to 1.25 and 1.3 fold by the simultaneous administration of ascorbic acid. Blood delta-aminolevulinic acid dehydratase (ALA-D) activity was decreased by 48.4 and 55.0 per cent with 5.0 and 10.0 mu moles cadmium treatment respectively; in the presence of ascorbic acid only 18 and 24 per cent inhibition of ALA-D activity was observed. Further 1.39 and 2.08 fold accumulation of delta-aminolevulinic acid and 4.17 and 4.62 fold increase of blood porphyrins was observed in chick embryos treated with 5.0 and 10.0 mu moles cadmium respectively. This elevation of intermediate compounds of heme biosynthesis was effectively checked by the administration of ascorbic acid. Depletion of hepatic heme and free sulfhydryl level by cadmium were countered by the treatment of ascorbic acid. Hence, the present findings suggest the protective role of ascorbic acid against cadmium induced chemical porphyria in chick embryos.

Topics: Animals; Ascorbic Acid; Cadmium; Chick Embryo; Dithiothreitol; Heme; Porphyrias

Protoporphyrinogen oxidase activity and ferrochelatase activity were measured in leucocytes from patients with porphyria variegata. The mean activity of protoporphyrinogen oxidase (PPO) in porphyria variegata (PV) was about 50% of normal (P less than 0.05). The mean activity of ferrochelatase with 59Fe2+ sulphate and protoporphyrin as substrates (in the presence of ascorbic acid) was reduced by 40% (P less than 0.009). The mean activity of ferrochelatase with 59Fe3+ chloride and protoporphyrin as substrates (in the presence of reduced glutathione) was increased by 65% (P less than 0.005). Both are statistically highly significant. The findings are interpreted as follows: (a) The occurrence of a low level of protoporphyrinogen oxidase in PV is confirmed. (b) The findings indicate a concurrent structural change in ferrochelatase (this may be structurally related to (a) but no evidence of this is at present available).

Topics: Adult; Ascorbic Acid; Chlorides; Female; Ferric Compounds; Ferrochelatase; Ferrous Compounds; Flavoproteins; Glutathione; Heme; Humans; Leukocytes; Lyases; Male; Middle Aged; Mitochondrial Proteins; Oxidoreductases; Oxidoreductases Acting on CH-CH Group Donors; Porphyrias; Protoporphyrinogen Oxidase; Protoporphyrins

The ascorbate status and the effect of loading doses of ascorbic acid (1,5 g per day by mouth for 7 days) on the porphyric process were studied in 7 black men with porphyria cutanea tarda symptomatica. It was found that the ascorbate stores were depleted in these patients as judged by serum and leucocyte ascorbate levels. Temporary repletion of the ascorbate stores was effected by the loading doses of ascorbic acid: Serum iron concentrations increased in 6 patients; urinary iron excretion showed small peaks a few days after ascorbic acid therapy commenced; haemoglobin concentration was not affected; excessive amounts of oxalate were excreted in the urine; neither total urinary porphyrin excretion nor the composition of the urinary porphyrins was affected in a way which could be related to ascorbate therapy. Further evidence that ascorbate depletion is not important in the induction of porphyria was found when the ascorbate status of siderotic rats, rendered porphyric by hexachlorobenzene-feeding, was examined. Stores of ascorbate and the oxidative catabolism of ascorbate were not different in the prophyric rats as compared with normal litter mates.

Topics: Adult; Animals; Ascorbic Acid; Female; Hemoglobins; Humans; Iron; Leukocytes; Male; Middle Aged; Oxalates; Porphyrias; Porphyrins

Topics: Ascorbic Acid; Erythropoiesis; Hemolysis; Humans; Porphyrias; Vitamin E

Topics: Adrenal Cortex Hormones; Adult; Ascorbic Acid; Eczema; Female; Humans; Male; Middle Aged; Niacinamide; Porphyrias; Prurigo; Vitamin B Complex

Topics: Adult; Ascorbic Acid; Equipment and Supplies; Erythrocytes; Hemolysis; Humans; Light; Nitrogen; Osmolar Concentration; Oxygen; Porphyrias; Potassium; Radiation Effects

Topics: Adenosine Triphosphate; Adult; Ascorbic Acid; Aspirin; Chelating Agents; Female; Glucocorticoids; Humans; Pantothenic Acid; Parasympatholytics; Porphyrias; Pyridoxine; Riboflavin; Sulfamethazine; Sulfhydryl Compounds; Thiamine Pyrophosphate; Time Factors

Topics: Animals; Ascorbic Acid; Barbiturates; Catalase; Diet; Humans; Lead Poisoning; Levulinic Acids; Lipid Metabolism; Liver; Magnesium; Mice; Mitochondria; Porphyrias; Purines; Rats

Topics: Anemia, Sideroblastic; Animals; Ascorbic Acid; Cobalt; Erythropoiesis; Erythropoietin; Humans; Lead Poisoning; Porphyrias; Porphyrins; Rats

Topics: Adult; Ascorbic Acid; Calcium; Dermatitis; Female; Humans; Light; Male; Middle Aged; Niacinamide; Porphyrias; Potassium; Prurigo; Riboflavin; Vitamins

Topics: Acetates; Amides; Ascorbic Acid; Barbiturates; Chlorobutanol; Dactinomycin; Ethionine; Fluorescence; Glucose; Hexachlorocyclohexane; Hypnotics and Sedatives; Metabolism; Oxidoreductases; Pharmacology; Porphyrias; Pyridines; Rats; Research; Sulfones; Urine

Topics: Animals; Ascorbic Acid; Chloroquine; Lagomorpha; Porphyrias; Rabbits; Thyroxine; Vitamins