Acute Iron Poisoning Research Articles

Diatom Chaetoceros Sp. as an Efficient Biological Antidote in Iron Toxicity: In‐Vitro and In‐Vivo Experiments

AbstractAll living organisms require mineral iron, but excess iron can lead to the production of free radicals and organ damage, such as liver damage in humans. This study investigated the diatom Chaetoceros sp. as an iron adsorbent in iron overload. First, the morphology and chemical composition of the diatom was characterized by spectroscopic and microscopic techniques. It was defined that diatoms have spherical particles with an average size of less than 2.0 μm. The affinity of diatoms for ionic Fe (II) uptake was evaluated. Fe (II) adsorption capacity was determined in vitro in two simulated intestinal and gastric aqueous media with pH values of 7.2 and 1.2. In both media, the diatom acted as a super‐adsorbent of Fe (II), while the highest adsorption occurred in a medium with a pH of 1.2. The correlation of the adsorption isotherm data was well studied with three well‐known equations, Langmuir, Fruindlich, and Redlich‐Peterson. The Langmuir model fitted the adsorption data best. The pseudo‐first‐order reaction model also provided a good fit for the adsorption kinetic data. In the in vivo study, the diatom was administered to iron‐overloaded rats. Biochemical parameters of organ damage and plasma Fe levels were determined at 2 h and 24 h intervals after diatom administration. The results show that diatoms can prevent acute iron poisoning by reducing plasma levels. Diatoms proved to be potent antidote agents in iron overdose conditions.

Near-fatal ferrous sulfate poisoning

Rationale: Acute iron poisoning is commonly seen in a pediatric population caused by accidental ingestion of iron syrups. We describe a case of iron poisoning who presented to the hospital following intentional near-fatal ingestion of ferrous sulfate. Patient’s Concern: A 14-years-old previously healthy female patient presented to the emergency department with a history of an intentional overdose of 80 ferrous sulfate tablets. Diagnosis: Ferrous sulfate poisoning. Interventions: The patient developed acute fulminant liver failure 24 h after of the overdose. She was managed conservatively, mainly with deferoxamine and N-acetylcysteine while awaiting transfer to a liver transplant facility. Outcomes: The patient responded well to medical therapy and was discharged on the 9th day of intensive care unit admission. Lessons: This case highlights the patient’s successful recovery with prompt conservative therapy. Severe iron toxicity can be treated with early use of deferoxamine and N-acetylcysteine where a liver transplant facility is not available.

Non-suicidal intentional ingestion of iron tablets and severe intoxication: the result of adolescent boy’s impulsive risky behaviour in the school

Acute iron poisoning is a potentially fatal intoxication in children. As the Iron preparations are commonly administered to pregnant women, lactating mothers, toddlers, it is easily available at home. So younger children are prone to consume it accidently. Although iron is a therapeutic drug in recommended dosages, excessive iron in the free state can produce toxicity by affecting multiple cellular processes by catalysing redox reactions with lipid peroxidation and free radical formation. The severity of intoxication depends on the amount of elemental iron ingested. Serious toxicity is usually associated with a dose of >40 mg/kg of elemental iron. Levels more than 100 mg/kg are almost always fatal. We report a case where a 12-year male child intentionally taken 60 tablets of iron (ferrous fumarate) at his school as a part of competition or bet to other schoolmate and presented with acute iron poisoning with hepatic encephalopathy to us. Important initial laboratory parameters were AST-4,879 U/L, Prothrombin time-60 sec and Iron level-213 microgram/dl. With timely specific management i.e., deferoxamine infusion along with all required intensive care supportive management in PICU the patient was discharged successfully. We chose to report this case to highlight the risky behaviour of adolescence who usually grows physically and emotionally earlier but their prefrontal lobes are yet immature to take proper and correct decision. Thus, impulse activity may prove fatal for them.

Designing of alternative polymeric nano-chelator for treatment in acute iron poisoning by molecular imprinting approach

The aim of this study is to develop an alternative polymeric chelating agent for rapid and selectively removal with high capacity of Fe3+ ions from the gastrointestinal tract for the oral treatment of acute iron poisoning. For this purpose, Fe3+ imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-(l)- glutamic acid) (HEMA-MAGA) nanoparticles synthesized by surfactant free emülsiyon polymerization. Molecular imprinting (MIP) technique is used to enhance the selectivity of nanoparticles. Due to being carboxyl and amide groups on the MAGA monomer, it was chosen as a chelating agent for Fe3+ ions. Before the synthesizing of Fe3+ imprinted polymer, Fe3+ ions were complexed with MAGA and then Fe3+ imprinted nanoparticles were synthesized in the presence of this Fe3+-MAGA complexes. Poly(HEMA-MAGA) nanoparticles were characterized by infrared spectroscopy (FTIR), atomic force microscopy (AFM). Average particle size and size distribution also determined by Zeta sizer. The specific surface area and mead diameter of the Fe3+ imprinted poly(HEMA-MAGA) nanoparticles was 895 m2.g-1 and 95.3 nm, respectively. The maximum Fe3+ ions binding capacity of the poly(HEMA-MAGA) nanoparticles at pH:4.0 were 206.4 mg.g-1 nanoparticles. Fe3+ removal performance of the Fe3+ imprinted poly(HEMA-MAGA) nanoparticles with presence of other ions, optimum medium pH, temperature and equilibrium binding time were also investigated. Fe3+ removal studies were performed in both aqueous solution and intestinal mimicking solution.The results indicate that Fe3+ imprinted poly(HEMA-MAGA) nanoparticles is an alternative chelating agent for the selective Fe3+ ions removal with a short time and very high capacity.

50 Years Ago in TheJournalofPediatrics: Exchange Transfusion for Acute Iron Poisoning: Current Status

50 Years Ago in TheJournalofPediatrics: Exchange Transfusion for Acute Iron Poisoning: Current Status

Efficacy of Intravenous N-acetylcysteine As an Adjuvant Therapy in Acute Iron Toxicity in Rats

Iron is a one of the heavy metals that is necessary for cell function. Acute or chronic exposure to high dose lead to oxidative damage. In the liver, iron overload affect hepatic mitochondrial respiration. Deferoxamine is the established antidote of iron toxicity which act as a chelator. N-acetylcysteine is a safe over the counter mucolytic which is antioxidant and glutathione substitute properities. Its use as an antidote for some toxins is well established nowadays. The aim of this work is to study the efficacy of intravenous N-acetylcysteine as an adjuvant therapy with deferoxamine in acute iron intoxication in rats. This study was carried out on twenty male albino rats, weighted 200-250 gm and divided into group I: 10 rats received 400 mg/kg elemental iron orally followed by 25 mg/kg subcutaneous deferroxamine and group II: 10 rats received 400 mg/kg elemental iron followed by 150 mg/kg IV NAC and 25 mg/kg subcutaneous deferroxamine. The results revealed that N-acetylcysteine use lowered both oxidative stress markers malondialdehyde MDA and cyclic adenosine monophosphate cAMP. On the other hand, the reduction of serum and hepatic iron levels and the elevation of Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) were statistically insignificant. It was concluded that intravenous N-acetylcysteine helps in reduction of oxidative stress caused by acute iron toxicity.

Minimum ingested iron cut‐off triggering serious iron toxicity in children

Iron intoxication can occur accidentally in children or intentionally by adolescents as a suicide attempt. They usually present with various symptoms including vomiting and diarrhea. Clinical studies in this field has been reported different doses of ingested elemental iron that caused serious toxicity, but none of these studies determined the minimum cut-off of ingested iron that triggered the risk of severe toxicity. The aim of this study was therefore to investigate the demographic features of iron intoxication in Turkish children and to determine the lowest cut-off of ingested elemental iron triggering serious intoxication and the need for prompt management. This retrospective study investigated 83 Turkish patients with accidental and intentional iron poisoning. Of the 83 cases of acute iron intoxication, accidental iron consumption was more common than intentional use. Fifty-three patients ingested a median toxic dose of elemental iron of 40.0mg/kg (IQR, 33.5mg/kg). The median serum iron concentration in the first 6h of ingestion was 150μg/dL (IQR, 282μg/dL). Twenty patients were given deferoxamine, whereas 63 patients were given supportive treatment. The cut-off of ingested elemental iron that triggered serious toxicity and the need for deferoxamine in children <18years of age was 28mg/kg.

Genome Sequencing of Streptomyces atratus SCSIOZH16 and Activation Production of Nocardamine via Metabolic Engineering.

The Actinomycetes are metabolically flexible microorganisms capable of producing a wide range of interesting compounds, including but by no means limited to, siderophores which have high affinity for ferric iron. In this study, we report the complete genome sequence of marine-derived Streptomyces atratus ZH16 and the activation of an embedded siderophore gene cluster via the application of metabolic engineering methods. The S. atratus ZH16 genome reveals that this strain has the potential to produce 26 categories of natural products (NPs) barring the ilamycins. Our activation studies revealed S. atratus SCSIO ZH16 to be a promising source of the production of nocardamine-type (desferrioxamine) compounds which are important in treating acute iron intoxication and performing ecological remediation. We conclude that metabolic engineering provides a highly effective strategy by which to discover drug-like compounds and new NPs in the genomic era.

P-396 - Novel third-generation ferrostatins protect against acute iron poisoning-induced organ injury

Ferroptosis is an iron dependent form of necrosis, involved in different pathologies such as kidney failure and neurodegenerative diseases. Glutathione peroxidase 4 (GPX4) is the central enzyme protecting the cell from ferroptosis. High-throughput screening led to the discovery of ferrostatin-1 (Fer-1) as a potent in vitro inhibitor of ferroptosis. In vivo however, the molecule suffers from instability. Therefore, we developed ferrostatin-analogues with improved solubility and in vivo stability. To verify their in vivo efficacy, we established an acute mouse model of iron poisoning-induced organ injury. Both an excess of the natural ferroptosis inhibitor vitamin E in the feed and overexpression of GPX4 have a protective effect on this iron poisoning model, indicating it is a valuable experimental model for ferroptosis-induced organ injury. Interestingly, our novel ferrostatin analogues effectively decrease several markers for organ injury after iron poisoning. Conclusively, 1) ferroptosis is a detrimental factor in acute iron poisoning, 2) our novel ferrostatin-analogues reduce the severity of organ injury due to acute iron poisoning, and 3) our third generation of ferrostatin-analogues might represent potential leads for the treatment of ferroptosis-driven pathologies.

Deferoxamine Preconditioning of Irradiated Tissue Improves Perfusion and Fat Graft Retention.

Radiation therapy is a mainstay in the treatment of many malignancies, but collateral damage to surrounding tissue, with resultant hypovascularity, fibrosis, and atrophy, can be difficult to reconstruct. Fat grafting has been shown to improve the quality of irradiated skin, but volume retention of the graft is significantly decreased. Deferoxamine is a U.S. Food and Drug Administration-approved iron-chelating medication for acute iron intoxication and chronic iron overload that has also been shown to increase angiogenesis. The present study evaluates the effects of deferoxamine treatment on irradiated skin and subsequent fat graft volume retention. Mice underwent irradiation to the scalp followed by treatment with deferoxamine or saline and perfusion and were analyzed using laser Doppler analysis. Human fat grafts were then placed beneath the scalp and retention was also followed up to 8 weeks radiographically. Finally, histologic evaluation of overlying skin was performed to evaluate the effects of deferoxamine preconditioning. Treatment with deferoxamine resulted in significantly increased perfusion, as demonstrated by laser Doppler analysis and CD31 immunofluorescent staining (p < 0.05). Increased dermal thickness and collagen content secondary to irradiation, however, were not affected by deferoxamine (p > 0.05). Importantly, fat graft volume retention was significantly increased when the irradiated recipient site was preconditioned with deferoxamine (p < 0.05). The authors' results demonstrated increased perfusion with deferoxamine treatment, which was also associated with improved fat graft volume retention. Preconditioning with deferoxamine may thus enhance fat graft outcomes for soft-tissue reconstruction following radiation therapy.

Çocuklarda Akut Demir Zehirlenmesi: Devam Eden Önemli Bir Pediatrik Acil

Objective: Iron containing drugs are one of the most commonly prescribed drugs in our country and accidental or suicidal poisoning continues to be an important pediatric emergency. Our aim was to evaluate the clinical, laboratory, radiologic findings, and treatment approaches of children hospitalized with acute iron poisoning. Material and Methods: The clinical, laboratory, and radiologic findings of and treatment approaches for 17 patients aged 14 months-15 years hospitalized with acute iron poisoning were reviewed. Results: The mean age was 37±35.2 months. Iron poisoning was accidental in 16 patients. The mean duration between drug intake and hospital admission was 177±149 minutes. The mean ingested amount of iron was 35.4±19 mg/kg. The mean blood iron level was 232±136 mcg/dl. There was no significant relationship between the reported dose of ingested iron and the blood iron level (p>0.05). There was no significant relationship between blood iron level and ingestion time (p>0.05). Laboratory results revealed metabolic acidosis in 3 patients, respiratory acidosis in one patient, leucocytosis in one patient, and prolonged activated partial thromboplastin time in one patient. The patients’ findings were not consistent with blood iron levels. Whole bowel irrigation and IV deferoxamine were used in 3 patients. There was no death. The mean hospitalization duration was 2.8±1.1 days. Conclusion: Accidental iron poisoning continues to be an important pediatric emergency. There are no correlations between blood iron levels and the amount of ingested iron or the ingestion time. There was also no correlation between the blood iron levels and the clinical, laboratory and radiographic findings in our study.

Intoxicação Aguda por Ferro: Uma Entidade Frequentemente Subvalorizada

Intoxicação Aguda por Ferro: Uma Entidade Frequentemente Subvalorizada

Augmentation of antioxidant and iron(III) chelation properties of tertiary mixture of bioactive ligands

The excess of iron in plasma and cellular compartment pose direct and indirect toxic effects. In the present investigation, we proposed additive function of nutritional bioactive ligands in combination which has shown enhanced antioxidant and iron(III) chelation property. The optimal interaction and in vitro antioxidant activity of tertiary mixture comprising of curcumin+quercetin+gallic acid was validated by central composite design (CCD) based on ferric reducing antioxidant power assay (FRAP). The additive denticity of nutritional bioactive ligands was investigated by UV–vis, FTIR & MALDI-TOF-MS analysis, which has given substantial evidence for the formation of tris-bidentate [curcumin-quercetin-gallic acid-Fe(III)] co-ordination complex. The in vivo proof of concept of the hypothesis was tested in iron intoxicated male wistar rats intoxicated with iron dextran. Co-administration curcumin+quercetin+gallic acid (CQG) exhibit dose dependent response & found effective in subsiding acute iron intoxication both at plasma and cellular level, evaluated by studies including serum ferritin, ICP-OES, lipid peroxidation and histopathology studies among others. Thus, we conclude that in vitro and in vivo studies supported our hypothesis to deduce additive function nutritional ligands to counteract direct and indirect effects of iron(III).

Is Ferriscan - a Useful Tool for Diagnosing and Monitoring Tissue Iron Load after Acute Iron Intoxication?

▪Almost 16,000 iron exposures annually are reported in children less than six years of age in the United States. Deferoxamine is the iron-chelating agent of choice. Deferoxamine binds absorbed iron, and the iron-deferoxamine complex is excreted in the urine. Indications for treatment include shock, altered mental status, persistent GI symptoms, metabolic acidosis, pills visible on radiographs, serum iron level greater than 500 µg/dL, or estimated dose greater than 60 mg/kg of elemental iron. No clear end point of therapy is distinguished. Infusion of deferoxamine for 6-12 hours has been suggested for moderate toxicity. For severe toxicity, administer deferoxamine for 24 hours. Because these end points are arbitrary, observe the patient for the recurrence of toxicity 2-3 hours after the deferoxamine has been stopped. Complications of iron toxicity include the following: Infection with Yersinia enterocolitica, acute respiratory distress syndrome (ARDS) and fulminant hepatic failure, hepatic cirrhosis, pyloric or duodenal stenosis. Systemic toxicity is expected with an ingestion of 60 mg/kg. Ingestion of more than 250 mg/kg of elemental iron is potentially lethal.Although a low serum ferritin is an accurate measure of iron deficiency, there is no accurate serum or plasma marker for acute body-iron overload. Serum iron concentration and transferrin saturation do not quantitatively reflect body iron. Stores and should therefore not be used as surrogate markers of tissue iron overload. Liver iron concentration provides the best measure of total body iron stores and is a validated predictor of the risks a particular patient faces from the complications of iron toxicity. Several imaging noninvasive techniques are available for measuring liver iron concentration (LIC) . There are two validated MRI methods for quantitating the liver iron burden: the FerriScan and T2 methods. The noninvasive R2-MRI technique (FerriScan) is highly sensitive and specific for estimating LIC and is approved by the Food and Drug Administration for routine clinical use. However, it was not used to diagnose and monitor LIC in cases of acute iron intoxication.This 27 year old female nurse by profession self-referred to hematology clinic for evaluation of Iron overload after self injecting herself with 20 ampoules of IV iron Ferro sac (each ampoule containing 200 mg of iron, (4000 mg elemental iron, 60 mg/kg) . Her CBC on presentation showed Hb of 12.5 g/dl her baseline Hb 9 g/dl with serum iron of 28 (NR 9.0 - 30.4 umol/L) ,TIBC of 42 NR(45 - 80 umol/L ), ferritin 1001 (NR 24-336 mcg/l)Her clinical exam was unremarkable. Her MRI showed severe iron overload. 9 mg /g dray tissue (NR 0.17-1.8) Patient received chelation with deferasirox at dose of 30 mg /kg for 6 months when her ferriscan showed almost normal LIC of 2 mg /g dry tissue.This case report showed the value of ferriscan in diagnosing the degree of tissue iron overload and in monitoring chelation to a safe level of hepatic iron content. DisclosuresNo relevant conflicts of interest to declare.

Clinical Approach to Acute Iron Poisoning: Case Series

Aim: Although acute iron poisoning is more common in the pediatric age, it may be seen at any age and is an important clinical condition. In this study, we aimed to evaluate the etiological factors and diagnosis and discuss treatment approaches in the acute iron poisoning. Material and Methods: Eight patients who were admitted to the intensive care unit due to acute iron poisoning were analyzed. Data regarding demographic features, cause of poisoning, toxic agents, the route of exposure, a history of previous toxicity, the time between exposure and intensive care unit admission, the owner of the poisoning agent (the patient or someone else), consciousness status on arrival, Glasgow coma score, the length of the intensive care unit stay, the result of laboratory tests, methods of treatment, and outcome were evaluated. Results: All 8 patients were female and the mean age was 22±5,4 years. The most common symptoms were abdominal pain, vomiting and diarrhea. The amount of received elemental iron was 30,25±11,4mg/kg. Nasogastric catheters were inserted and gastric lavages were performed to all the patients in the emergency department. Deferoxamine treatment was not implemented because of serum iron levels were not higher than 500 mg / dL. After observing all patients for two days, one patient was transferred to psychiatric clinic, 7 patients were discharged with full recovery. Conclusions: In potentially fatal acute iron poisoning, serious complications can be avoided with early laboratory and clinical follow-up. The basic supportive therapy with gastric lavage and desferroksamine therapy should be managed on time. Key Words: Acute Iron Poisoning; Intensive are; Deferoxamine.

Acute iron intoxication: change in urine color during chelation therapy with deferoxamine

Acute iron intoxication: change in urine color during chelation therapy with deferoxamine

Successful Treatment of Severe Iron Intoxication with Gastrointestinal Decontamination, Deferoxamine, and Hemodialysis

Acute iron poisoning is a common and potentially serious problem in the pediatric population. Early recognition and treatment is crucial for a better outcome and to prevent morbidity and mortality. An 18-year-old female, who had accidental ingestion of 50 tablets of ferrous sulfate (100 mg of elemental iron per 335 mg tablet), 100 mg/kg of elemental iron, developed acute gastrointestinal and neurologic signs of toxicity and severe anion gap metabolic acidosis. The patient had received gastrointestinal decontamination, deferoxamine (DFO) infusion, and hemodialysis (HD) resulting in a decrease in serum iron concentration from 2150 to 160 mcg/dL at 24-h post-ingestion and improved mental status. Our cases demonstrate that HD may assist in decreasing serum iron concentration and improving clinical status in patients with massive overdose and life-threatening toxicity.

Dephosphorylation Reactions of Mono-, Di-, and Triesters of 2,4-Dinitrophenyl Phosphate with Deferoxamine and Benzohydroxamic Acid

This work presents a detailed kinetic and mechanistic study of biologically interesting dephosphorylation reactions involving the exceptionally reactive nucleophilic group, hydroxamate. We compare results for hydroxamate groups anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the more complex structure of the widely used drug, deferoxamine (DFO). BHA shows extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection of the phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of the nucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groups and shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests a potential use for DFO in cases of acute poisoning with phosphorus pesticides.

High hepcidin level accounts for the nigral iron accumulation in acute peripheral iron intoxication rats

Hepcidin is considered to be a circulatory hormone and a major mechanism regulating iron homeostasis. Our previous publication revealed that acute iron intoxication induced iron deposit and dopaminergic neuron degeneration in the substantia nigra (SN) of a rat model. However, whether and how hepcidin functions in this nigral iron accumulation has not been elucidated. In the present study, we observed a decreased of FPN1 protein level in the SN triggered by peripheral iron overload within 4h, which correlated with a high hepcidin level. To further investigate the role of intracellular hepcidin under iron overload circumstances, we assessed the expression of hepcidin mRNA and FPN1 protein in vitro. We observed that hepcidin mRNA level was up-regulated and FPN1 protein level was down-regulated in MES23.5 dopaminergic cells in a period of 4h incubation with iron. Both in pCMV-XL4-hepcidin transfected and hepcidin-treated cells, decreased FPN1 protein levels were observed. Our data provide direct evidence that the role for intracellular hepcidin generated in the SN is particularly relevant to restrict iron release by down-regulation FPN1 expression in this region, thus an important contributor to the abnormal iron deposit occurred at an early stage in conditions of peripheral iron intoxication.

Intraperitoneal N-acetylcysteine for acute iron intoxication in rats

Free radical formation and release of oxidant agents have been suggested as possible mechanisms for tissue damage in acute iron intoxication. N-acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used as an antidote for various intoxications. Our aim was to determine whether intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic oral doses of iron. Male Wistar rats were studied in three phases. In the first phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p. NAC) and observed for survival. In the second phase, rats were assigned to groups 3 (400 mg/kg elemental iron orally) and 4 (400 mg/kg elemental iron, followed by 150 mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died within 90 minutes after iron administration, a third phase was conducted in order to allow for comparison of iron and transaminase serum levels after the administration of iron and NAC (group 5: n = 10). Mortality was significantly lower in rats treated with iron and NAC, compared to those treated with iron (P = 0.016). Median serum iron level was significantly lower among rats treated with iron and NAC, compared with rats treated with iron alone (P = 0.002). In a rat model of acute iron intoxication, i.p. administration of NAC may decrease serum iron levels and mortality.