Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda.

UNLABELLED: Porphyria cutanea tarda is a liver disease characterized by elevated hepatic iron and excessive production of uroporphyrin (URO). Phlebotomy is an effective treatment that probably acts by reducing hepatic iron. Here we used Hfe(-/-) mice to compare the effects on hepatic URO accumulation of two different methods of hepatic iron depletion: iron chelation using deferiprone (L1) versus iron-deficient diets. Hfe(-/-) mice in a 129S6/SvEvTac background were fed 5-aminolevulinic acid (ALA), which results in hepatic URO accumulation, and increasing doses of L1 in the drinking water. Hepatic URO accumulation was completely prevented at low L1 doses, which partially depleted hepatic nonheme iron. By histological assessment, the decrease in hepatic URO accumulation was associated with greater depletion of iron from hepatocytes than from Kupffer cells. The L1 treatment had no effect on levels of hepatic cytochrome P4501A2 (CYP1A2). L1 also effectively decreased hepatic URO accumulation in C57BL/6 Hfe(-/-) mice treated with ALA and a CYP1A2 inducer. ALA-treated mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria, even when the animals were iron-supplemented either directly in the diet or by iron dextran injection. CONCLUSION: The results suggest that dietary factors other than iron are involved in the development of uroporphyria and that a modest depletion of hepatocyte iron by L1 is sufficient to prevent URO accumulation.

Effect of high fiber vegetable-fruit diet on the activity of liver damage and serum iron level in porphyria cutanea tarda (PCT).

BACKGROUND: During the treatment of coronary heart disease with a vegetable-fruit diet, we have observed the positive effect of the treatment on PCT patients. Therefore, we have now examined the short-term results of the diet on the selected PCT activity parameters. The study was approved by our Review Board. MATERIAL AND METHODS: A group of 13 male PCT patients (mean age 52 years) was evaluated. We assessed the body mass index (BMI), serum iron level, activity of transaminases (ALT, AST), severity of skin symptoms, and urinary prophyrins excretions, before and after a three-week period of vegetable-fruit diet. The diet was of natural vegetable/fruit products, and its daily caloric content was ca. 500 kcal/day. RESULTS: The mean BMI before and after the diet period were 26.8 +/- 4.7 vs. 25.8 +/- 4.3 (p = 0.001), the serum activities of ALT 122.0 +/- 60.7 U/l vs. 75.6 +/- 31.8 U/l, and of AST 91.8 +/- 56.0 U/l vs. 55.2 +/- 14.2 U/l (p = 0.001), respectively. The mean serum iron levels were 188.6 +/- 75.7 mg/dl vs. 140.2 +/- 56.4 mg/dl, serum ferritin concentrations 574 +/- 351 vs. 499 +/- 340 ng/ml (p = 0.04), respectively. Severity of skin lesions and urinary coproporphyrins excretion were significantly diminished during the diet; urinary uroporphyrins excretion was also lowered, but not to a statistically significant level. CONCLUSION: In our group of PCT patients, we noticed the beneficial effect of the vegetable-fruit diet on selected disease parameters. The diet may be useful in the treatment of PCT and diseases associated with PCT.