Effect of Ascorbic Acid on Desferrioxamine-Induced Urinary Iron Excretion in Idiopathic Hemochromatosis

Conte, Dario; Brunelli, Lucia; Ferrario, L; Mandelli, C.; Quatrini, M; Velio, P.; Bianchi, Paolo

doi:10.1159/000206370

Cited by 12 publications

(8 citation statements)

References 10 publications

(15 reference statements)

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“…79 Chronic uncontrolled HH is associated with hepatomegaly, micronodular cirrhosis, cardiomyopathy, arthritis, gastric and duodenal siderosis, osteopenia, abnormal cutaneous pigmentation, hepatocellular carcinoma, diabetes, and hypogonadism. 1,9,17,20,30,55,72,74,79 The clinical signs of HH are probably due to abnormally high uptake of dietary iron in the duodenum. 20 Three inherited forms of human hemochromatosis are now recognized.…”

Section: Discussionmentioning

confidence: 99%

“…1,9,17,20,30,55,72,74,79 The clinical signs of HH are probably due to abnormally high uptake of dietary iron in the duodenum. 20 Three inherited forms of human hemochromatosis are now recognized. The most common is HFE-related hemochromatosis (hemochromatosis type 1), where the majority of patients are homozygous for the C282Y mutation of the HFE gene on chromosome 6.…”

Section: Discussionmentioning

confidence: 99%

“…In affected cattle, differences include greater amounts of iron in duodenal and gastric mucosa, more extensive mineralization of collagen, elastin, and reticulin, earlier onset, more rapid clinical progression, presence of renal lesions, minimal cardiac lesions, and females rather than males being more commonly identified. 1,19,20,24,36,72 Five of the six Salers cattle had a panacinar rather than a portalto-centrilobular (acinar zones 1-3) gradient of iron accumulation typical of HH. 11,52,72 These differences may be due to species-determined differences in normal iron metabolism or may reflect a fundamentally different pathogenesis for iron overload.…”

Section: Discussionmentioning

confidence: 99%

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Hepatic Failure and Hemochromatosis of Salers and Salers-cross Cattle

et al. 2001

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Abstract. Hemochromatosis is rare in domestic mammals. Five clinical cases and one preclinical case of hemochromatosis were diagnosed in Salers and Salers-cross cattle. Clinical disease developed between 9 and 22 months of age. Animals were healthy until weaning but then lost weight, developed rough hair coats, and lost incisor teeth. In two animals, hemochromatosis was identified by liver biopsy, biochemical evidence of hepatic injury, and/or elevated transferrin saturation values. At necropsy, carcasses were thin, with firm dark brown livers and lymph nodes, soft bones, and brown-colored small bowel. The principal histologic changes were hepatocellular siderosis and periportal, bridging, and perivenular fibrosis. Siderocalcinosis involved collagen, elastin, reticulin, and basement membrane components in liver, lymph nodes, spleen, duodenum, and kidney. Hepatic iron concentrations in clinically affected cattle were 1,500-10,500 g/g wet weight (reference range for cattle ϭ Ͻ300 g/ g). Ultrastructurally, the heaviest intrahepatic deposition was in hepatocytes, which contained large intracytoplasmic siderosomes. Iron deposition in bone was associated with osteopenia. Genetic analysis indicated a common ancestral bull in the pedigrees of five of six affected cattle; no pedigree was available for the remaining animal. Four dams of five affected animals were phenotypically normal and had histologically normal livers. Test mating of four cows to the ancestral bull resulted in a female calf that developed clinicopathologic and histologic evidence of preclinical hemochromatosis by 40 days of age. It was not possible to establish the pattern of inheritance because of the small number of pedigrees from affected cattle.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hepatic Failure and Hemochromatosis of Salers and Salers-cross Cattle

et al. 2001

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“…Similar effects were observed in idiopathic haemochromatosis patients, where increasing doses of 0.2 to 2.0 g of ascorbic acid were shown to cause progressive increases in iron excretion. Furthermore, it was also confirmed that ascorbic acid is not effective in increasing iron excretion without the use of deferoxamine [ 197 ]. Current protocols for the optimization of iron excretion caused by deferoxamine in thalassaemia and other transfusional iron loaded conditions involve the oral administration of a total of 400 mg; 200 mg before and 200 mg during the subcutaneous infusion of deferoxamine.…”

Section: The Role Of Ascorbic Acid In Iron Absorption and Iron Excmentioning

confidence: 99%

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

et al. 2020

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Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.

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“…20,21 In addition to antioxidant monotherapy, the combination of an antioxidant and an iron chelator could provide enhanced and increased therapeutic benefits to improve organ function by decreasing tissue iron accumulation and reduce oxidative stress in iron overload conditions. A combination of vitamin C with an iron chelator was shown to significantly increase urinary iron excretion (UIE), 65,66 and increase LVEF 67 in idiopathic hemochromatosis, beta-thalassemia major (β-TM) and adult non-thalassemic patients with transfusional iron overload, and also improve the biochemical and histopathological cardiac changes in ironoverloaded rats. 68 However, the use of vitamin C has been raised as a serious concern since it may induce iron toxicity by altering the Fe 3+ ion to Fe 2+ , the toxic form, which leads to increased enterocyte iron absorption and increased iron release from the macrophages of the reticuloendothelial system.…”

Section: Oxidative Stressmentioning

confidence: 99%

Iron overload cardiomyopathy: Using the latest evidence to inform future applications

Kumfu

Chattipakorn

2022

Exp Biol Med (Maywood)

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Iron overload can be the result of either dysregulated iron metabolism in the case of hereditary hemochromatosis or repeated blood transfusions in the case of secondary hemochromatosis (e.g. in β-thalassemia and sickle cell anemia patients). Under iron overload conditions, transferrin (Tf) saturation leads to an increase in non-Tf bound iron which can result in the generation of reactive oxygen species (ROS). These excess ROS can damage cellular components, resulting in the dysfunction of vital organs including iron overload cardiomyopathy (IOC). Multiple studies have demonstrated that L-type and T-type calcium channels are the main routes for iron uptake in the heart, and that calcium channel blockers, given either individually or in combination with standard iron chelators, confer cardioprotective effects under iron overload conditions. Treatment with antioxidants may also provide therapeutic benefits. Interestingly, recent studies have suggested that mitochondrial dynamics and regulated cell death (RCD) pathways are potential targets for pharmacological interventions against iron-induced cardiomyocyte injury. In this review, the potential therapeutic roles of iron chelators, antioxidants, iron uptake/metabolism modulators, mitochondrial dynamics modulators, and inhibitors of RCD pathways in IOC are summarized and discussed.

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Effect of Ascorbic Acid on Desferrioxamine-Induced Urinary Iron Excretion in Idiopathic Hemochromatosis

Cited by 12 publications

References 10 publications

Hepatic Failure and Hemochromatosis of Salers and Salers-cross Cattle

Hepatic Failure and Hemochromatosis of Salers and Salers-cross Cattle

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

Iron overload cardiomyopathy: Using the latest evidence to inform future applications

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