Naringin is a promising natural compound for therapy of iron-overload disorders

Abstract Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. 35 mice were classified into five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then treated with normal saline (as control), naringin or DFO Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl's staining. The results revealed that naringin is more potent than DFO in removing excessive iron ions deposited in liver tissues, indicating that naringin is a promising natural compound for therapy of iron overload disorders

Bilateral maculopathy in a thalassemia patient on iron chelation therapy: a case report / Maculopatia bilateral em paciente com talassemia em terapia quelante de ferro: relato de caso

ABSTRACT A 10-year-old Malay girl with underlying HbE/beta-thalassemia, on regular blood transfusion and deferoxamine iron chelation therapy, presented with two-month history of bilateral blurring of vision. On examination, her vision was 6/36 both eyes. Other optic nerve functions were normal. Anterior segment examination of both eyes was unremarkable. Fundus examination of both eyes revealed dull foveal reflex. Optical coherence tomography of both maculae showed increased central subfield thickness. Fundus fluorescence angiography showed patchy hypofluorescence over macular region for both eyes and late staining, indicating retinal pigment epithelium anomalies. A diagnosis of iron-chelation-therapy-related bilateral maculopathy was made. Patient was co-managed with pediatric hematology team to adjust the dose of deferoxamine, and was given three monthly appointments to monitor the progression of maculopathy at the ophthalmology clinic. However patient defaulted ophthalmology follow-up after the first visit.

RESUMO Uma menina malaia de 10 anos de idade com doença de base- B/beta-talassemia, em transfusão de sangue regular e terapia quelante de ferro deferoxamina, apresentou história de dois meses de visão turva bilateral. Ao exame, sua visão era de 6/36 em ambos os olhos. Outras funções do nervo óptico estavam normais. O exame do segmento anterior de ambos os olhos foi normal. Exame do fundo de ambos os olhos revelou reflexo foveal opaco. A tomografia de coerência óptica de ambas as máculas mostrou aumento da espessura do subcampo central. A angiografia de fluorescência do fundo mostrou hipofluorescência irregular sobre a região macular de ambos os olhos e coloração tardia, indicando anomalias de epitélio pigmentar da retina. Um diagnóstico de maculopatia bilateral relacionada à terapia quelante de ferro foi feito. A paciente foi avaliada em conjunto com a equipe de hematologia pediátrica para ajustar a dose de deferoxamina, e foram oferecidas três consultas mensais na clínica oftalmológica, para monitorar a progressão da maculopatia. No entanto, ela não compareceu para acompanhamento oftalmológico após a primeira visita.

Cardiac events and cardiac T2[*] in Egyptian children and young adults with beta-thalassemia major taking deferoxamine

Cardiac events and death are not uncommon in adults with beta-thalassemia [beta-TM] taking deferoxamine [DFO] monotherapy because of poor compliance and possibly the less effectiveness of DFO in controlling cardiac iron overload. We sought to assess compliance with DFO, the percentage of shift to other iron chelators, and the occurrence of cardiac siderosis, and cardiac events and death in beta-TM patients on DFO monotherapy. Prospective, observational, 10-year follow-up of patients attending Ain Shams Thalassemia Unit, Cairo, Egypt. For all beta-TM patients aged 2-1 8 years attending the unit during January 1998 and taking DFO, we recorded all cardiac events [whether fatal or not] during January 2008. All patients still on DFO monotherapy and with a normal EKG and not showing symptoms or signs suggestive of heart failure [HF] were evaluated for cardiac siderosis byT2[*]. Of 412 patients, only 126 [31%] were still taking DFO monotherapy [only 43% of those were compliant], 136 were taking combined DFO and deferiprone [DFP], 72 were taking DFP and 32 were taking deferasirox [DFX]. Twenty-one were lost follow-up and 25 died [10 cardiac]. Eight of ten cardiac deaths and 12 of 15 non-cardiac deaths were in the DFO monotherapy group. Those taking DFO monotherapy with no HF and left ventricular ejection fraction [LVEF] by T2[*] >56% had a median age of 19 years and 56% were males; cardiac T2[*] was <20 ms in 30 [22%]; 10-20 ms in 20 [14.7%] and <10 ms in 10 [7.3%]. LVEF ranged from 58%-76% [median 64%]. Forty percent of T2* patients <10 ms were compliant with DFO. Fifty-eight percent of patients on DFO monotherapy were noncompliant, but even compliance did not prevent severe cardiac siderosis and most cardiac events [whether fatal or not] that occurred in the DFO monotherapy group

Rapid iron loading in heart and liver in a patient with transfusion dependent thalassaemia after brief poor compliance with iron chelation therapy

Iron loading in patients with transfusion dependent thalassaemia is considered to occur primarily in the liver and, once the liver becomes saturated, other organs begin loading. We report here a splenectomised male patient who was treated for hepatitis C virus infection. Prior to starting antiviral therapy, his serum ferritin was maintained below 500 ng/ml with deferiprone monotherapy; cardiac T2[*] by magnetic resonance imaging was 48.8ms and hepatic T2[*] was 19.5ms. After twelve months of antiviral treatment during which time he was very poorly compliant with his deferoxamine chelation therapy, his ferritin had risen to 3820 ng/ml and cardiac and hepatic T2[*] findings were 12.7 ms and 14.5 ms respectively, indicating increased iron loading in both organs, but particularly in the heart. Fifteen months after recommencing combination chelation, his ferritin was 95 ng/ml and cardiac and hepatic T2[*] were 27.5 and 28.4ms respectively, indicating complete clearance of iron load in both organs. This case demonstrates that iron overload can develop rapidly and in some cases there is relatively rapid iron loading in the heart as compared to the liver

[Evaluation of hearing loss and otolaryngeal disorders in beta thalassemic patients treated with desferrioxamine]

Thalassemia is one of the most prevalent heamoglobinopathies in the world in particular in Iran. Major thalassemia patients need blood transfusion and desferrioxamin injections throughout their life. Regarding improved life quality of thalassemic patients, new clinical problems, such as hearing loss, need more attention. This study was done to determine the frequency of hearing loss and otolaryngeal disorders together with their related factors in major beta thalassemic patients. This was a descriptive analytic study and 84 beta thalassemia patients were examined and evaluated for hearing loss by an otolaryngologist. Standard pure tone audiometry was performed for the patients. Serum ferritin level was measured. Considering blood transfusion the patients were divided into two groups: those with suitable transfusions and those with unsuitable transfusions. Also in regard to desferrioxamin injections again the patients were divided into two groups: those with regular injections and those with irregular injections. Among 84 beta thalassemic patients [40 M, 44 F] with mean age of 12.8 +/- 5.7 years, 10 [11.9%] had sensorineural hearing loss, 8 [9.5%] had conductive hearing loss, while 8 [9.5%] showed mixed hearing loss. There was no relationship between hearing loss and age, sex, ferritin level, but hearing loss had a significant relationship with doses and duration of desferrioxamine therapy [P<0.01]. Also hearing loss had no significant relationship with regular and irregular blood transfusions and desferrioxamine injections [P<0.01]. The results of this study implicated that high dose desferrioxamine was the main factor in the pathogenesis of ototoxicity in thalassemic patients. For management of these patients it is necessary to use proper doses of desferoxamine. Also blood transfusions should be proportional to body iron burden and hemoglobin. In addition, regular periodic otolaryngologic and audiometric follow up examinations are required for early diagnosis of hearing disorders in prevention of permanent hearing loss

influence of iron loading and iron chelation on the proliferation and telomerase activity of human peripheral blood mononuclear cells

Iron is an essential trace element in cell proliferation. Several investigations demonstrate that iron deprivation inhibits cell proliferation. However, the impact of iron on telomerase activity of activated lymphocytes remains unexplained to date. In this study, the effect of iron on the proliferation and telomerase activity of lymphocytes stimulated by phytohemagglutinin [PHA] were investigated. Iron loading was performed by incubating peripheral blood mononuclear cells in 500 micro M FeSO[4].7H[2]O for 24 h and iron chelation was done by exposing cells to desferrioxamine, a potent iron chelator. The effects of silymarin, a flavonoid with both antioxidant and iron chelating activities, on the proliferation and telomerase activity of PHA-activated lymphocytes were also compared with desferrioxamine. Proliferation and telomerase activity were assessed using BrdU incorporation assay and Telomeric Repeat Amplification Protocol [TRAP], respectively. The proliferations of lymphocytes were significantly inhibited by 10 and 20 micro g/ml desferrioxamine in a dose dependent manner, while iron loading recovered suppressed cell proliferation to the normal level. Silymarin at 20 micro g/ml significantly increased the proliferation of lymphocytes in both normal and iron-treated conditions. Telomerase activity of lymphocytes was markedly increased by iron treatment and suppressed by desferrioxamine. Conversely, iron treatment had no effect on the telomerase activity of lymphocytes incubated with silymarin. Iron plays a significant role in the proliferation and telomerase activity of lymphocytes. The effects of silymarin on the proliferation and telomerase activity of lymphocytes were completely different from those of desferrioxamine, suggesting that the immunomodulatory effect of silymarin is probably not associated with its iron chelating activity

Assess the knowledge and practice of thalassemic patient about complications of iron overload and desferal compliance

To assess the knowledge and practice of thalassemic patients about desferal administration and complications of iron overload. The present study composed of [50] thalssemic patient who are registered in center and was performed in Ibn AI-Atheer center for congenital anemia for the period from 15/12/2006 to 1/4/2007. The result of the study showed highly significant difference at [P<0.05] for knowledge of thalassemic patients and also appear highly significant difference at [P<0.05] for practice of thalassemic patients. The study recommends that there is necessity to increase the knowledge and practice of thalassemic patient about desferal administration to minimize the complications of iron overload

Visual function evaluation of Egyptian beta-thalassemia major patients on long-term desferal therapy

The success of the iron chelator desferal [DFO] in the treatment of beta - thalassemia is limited by its lack of bioavailability. Also, high dosage has been associated with toxicity of the eyes, ears and others. To investigate a possible subclinical visual neurotoxicity, 30 Egyptian p-thalassemia major [BTM] patients on long-term, recommended DFO dosage were studied using visual evoked potentials [VEPs] and electroretinogram [ERG]. We also aimed to clarify the relation of the possible abnormalities to various clinical, hematologic and biochemical parameters. Ten healthy age - matched individuals were enrolled as controls. Sixteen/30 [53.3%] patients showed subclinical abnormalities using VEP and/or ERG. Nine/30 [30%] had VEPs abnormalities, 10 [33.3%] had ERG abnormalities and 3 [10%] revealed abnormalities by both methods. An interesting observation was the significant association of abnormal VEP and MALE sex [P=0.0002]. No significant correlation was found between neurophysiologic abnormalities and all data studied as: age, frequency of blood transfusion, DFO dosage/ duration, splenectomy, CBC values; S. ferritin, Serum Copper, S. Zinc and S. vitamin E. A single patient could have subclinical DFO-induced visual toxicity using VEP as his "toxicity" index [TI] was high [0.078]. the abnormalities can not be mostly attributed to long-term DFO therapy. Serial visual monitoring [including VEP and ERG] of all BTM patients is warranted. It is worthwhile to compare the long-term toxicity of the oral chelating agents [e.g. L 1 and ICL670] with that of DFO before definite conclusions are drawn on any visual neurotoxicity and its relation with the disease state or drug therapy

Survey on relation between major thalassemia and desferiexamine with renal tubular damage

Thalassemia is a hereditary quantitative hemoglubinopathy which is common in mediteranian area including IRAN. Homos zygotic beta thalassemia patients suffer from severe anemia and complication of the disease in many organs. Studies have shown different results about renal complication and disease. Thus, in this study we investigated renal function of thalassemia Major [TM] patients in comparison with control group. This was a historical cohort Study. The population who TM patients was were admitted to Boalisina hospital, Sari, and control group were brothers and sisters of the patients who were matched in gender and age. Serum and urine markers of renal function were measured and demographic and therapeutic data were gathered from medical records. Analysis of the data was performed using SPSS 11 with statistical test [t, chi square]. The Total of 84 [42 patients and, 42 controls] patients were studied. The Mean age of the patients was 21.3 +/- 5.2 years. Dose of Deferral was 70 +/- 19 mg/kg. The results showed no significant statistical differences in levels of beta2 microglobulin, 24 urine protein, Excretion Fraction of Na and K between case and control group. There was significant differences in levels of serum BUN, creatinin, Potassium and urine potassium and creatinin between case and control group. Gender, level of Hb and serum Ferritin significantly affected the differences between two groups. In this study, evidences of renal tubular damage were not detected in TM patients. There was increase in levels of Bun, serum potassium, uric Acid, specially with severe anemia, high dose desferal and Iron over load

effectiveness of an educational intervention on maternal management of children with beta thalassemia

Beta thalassemia causes significant morbidity and mortality in the affected individual and a traumatic burden to other family members. Increasing the ability of the child for self care and proper maternal management, in addition to proper counseling are expected to have good impact on disease management and prevention. The purposes of this study are to identify deficits in maternal management of children with beta-thalassemia, to implement an educational intervention to help mothers to improve and increase self care capabilities and to evaluate the effectiveness of the educational intervention on mothers' knowledge, maternal management, serum ferritin level and length of hospitalization. The study was conducted at two rooms assigned to thalassemic children in the pediatric surgical ward of New Sohar Hospital. A convenient sample of 38 children with beta- thalassemia was included. Their age ranged between 6 month and 16 years; all of them undergo chelation therapy. Interview questionnaire sheet and observation checklist were used to collect data as a pre- post test to assess maternal management of desferal. Data were collected in different 4 phases: initial phase, development of educational intervention, implementation and evaluation phase. All mothers did not have any knowledge about components and function of blood at the pre test and their knowledge improved after one month in 78%, and 68.4% retained it after 3 months. Likewise, knowledge in the area of causes and prognosis of the disease has improved from 36.84% at the pretest to 94.74% immediately and after 3 month. Also mothers' knowledge about hygiene improved significantly. None of the mothers had correct knowledge before educational intervention neither about the amount of iron in the body nor about diets that increase iron absorption and only 28.9% gave correct answer about the problems of iron overload. The percentage improved significantly after educational intervention: 97.4% immediately and after 3 months. Correct answer in the pre test about when to give desferal was given by 28.9%; and their percentage improved to become 76% immediately and 71% after 3 months. At pretest, none of mothers were able to administer desferal by themselves; while immediately after intervention, 97.4% became able. However this percentage dropped to 76% after 3 months. Meanwhile, the mothers' compliance improved after the educational intervention. When comparing the reported side effects of administering desferal, 52.6% in pretest reported lump formation at the site of injection compared to only 2.6 after intervention. Mentioning abscess formation decreased from 15.7 to zero. After 3 months, none of them reported these side effects and the difference was statistically significantly. Also mothers' management of side effects of desferal had improved significantly. A marked decrease of the serum ferritin was noticed at the post test and the difference was significant than pre test. The frequency and length of hospitalization have significantly dropped after educational intervention. beta-thalassemia requires prolonged regiment of management and care. For the care to be effective, mothers and children need continuous support, understanding, and frequent interview to reinforce the positive behavior and keep refining their knowledge through educational intervention. Premarital counseling is highly needed, social and professional support is highly recommended

Efeito da deferoxamina na isquemia e reperfusäo do fígado remanescente após ressecçäo hepática parcial / Effect of deferoxamine in ischemia and reperfusion remaining after partial hepatic resection

Particularmente, a utilização de vários tipos de drogas que diminuem os efeitos deletérios do binômio isquemia-reperfusão, tem tornado-se foco de vários estudos experimentais visando possíveis aplicações clínicas. O objetivo do presente estudo foi avaliar os efeitos da deferoxamina na isquemia e reperfusão sobre o fígado remanescente após ressecção hepática parcial a 70 por cento, avaliando-se váriáveis bioquímicas do sangue: aspartato aminotransferase e alanina aminotransferase;.A amostra de 34 ratos foi dividida em grupos: Grupo HP (n = 8) - submetidos a hepatectomia parcial (HP) a 70 por cento; Grupo HPD (n = 4) - submetidos a administração de deferoxamina (40 mg/kg) e HP a 70 por cento; Grupo HPI (n = 7) - hepatectomizados (HP a 70 por cento) e submetidos a isquemia (40 minutos); Grupo HPID (n = 7) - semelhante ao anterior, porém recebendo previamente deferoxamina; Grupo C (n = 8) - controle, submetido a operação simulada para HP a 70 por cento. A análise estatística entre os diversos grupos foi feita pelos testes de Kruskal - Wallis e de Mann - Whitney, com nível de significância de 5 por cento. Portanto, houve aumento significativo das aminotransferases nos animais submetidos a hepatectomia e a isquemia. Esse aumento foi inibido pela deferoxamina.