RESUMEN

Acute iron overload is known to exert deleterious effects in the liver, but detailed pathology has yet to be documented. Here, we report pathological findings in an autopsy case of acute iron toxicity and validation of the findings in mouse experiments. In a 39-year-old woman who intentionally ingested a large amount of sodium ferrous citrate (equivalent to 7.5 g of iron), severe disturbance of consciousness and fulminant hepatic failure rapidly developed. Liver failure was refractory to treatment and the patient died on Day 13. Autopsy revealed almost complete loss of hepatocytes, while bile ducts were spared. To examine the detailed pathologic processes induced by excessive iron, mice were orally administered equivalent doses of ferrous citrate. Plasma aminotransferase levels markedly increased after 6 h, which was preceded by increased plasma iron levels. Hepatocytes were selectively damaged, with more prominent damage in the periportal area. Phosphorylated c-Jun was detected in hepatocyte nuclei after 3 h, which was followed by the appearance of γ-H2AX expression. Hepatocyte injury in mice was associated with the expression of Myc and p53 after 12 and 24 h, respectively. Even at lethal doses, the bile ducts were morphologically intact and fully viable. Our findings indicate that acute iron overload induces hepatocyte-specific liver injury, most likely through hydroxyl radical-mediated DNA damage and subsequent stress responses.

RESUMEN

OBJECTIVE: Iron poisoning is a historically important cause of paediatric morbidity and mortality. In recent decades, public health measures have considerably reduced paediatric iron exposures. We investigated unintentional paediatric iron poisoning in children with the aim of developing an assessment approach specific for this group. METHODS: This was a retrospective observational study of unintentional iron poisoning in children (<7 years old) referred to either a state-wide poisons information service or a tertiary clinical toxicology unit from 1 January 2015 to 16 February 2020. Patients were identified from prospective databases maintained by both services, and data were extracted from these in addition to the medical record. RESULTS: There were 54 children included in the study (29 [54%] male; median age 2 years (range 8 months to 4 years). The median suspected dose of elemental iron ingested was 72 mg/kg (IQR 41-140 mg/kg). Seventeen (31%) children were symptomatic. There were no cases of severe toxicity. Children symptomatic with gastrointestinal toxicity had a median suspected dose ingested of 60 mg/kg (IQR 38-150 mg/kg) that was similar to asymptomatic children (81 mg/kg [IQR 41-143 mg/kg], P = 0.809). The median peak iron concentration was 49 µmol/L (IQR 13.5-67.5 µmol/L, range 4-75 µmol/L). Symptomatic children had a significantly higher median peak serum iron concentration of 66 µmol/L (IQR 54-68 µmol/L) compared to 12 µmol/L (IQR 9-15 µmol/L) in asymptomatic children (P < 0.001). CONCLUSION: Unintentional paediatric iron poisoning is uncommon and largely benign. Suspected dose ingested is a poor predictor of toxicity. Targeting investigations and interventions to symptomatic children should reduce unnecessary assessment and management while still safely managing the exposure.

Asunto(s)

RESUMEN

BACKGROUND: The pathogenesis of chemotherapy-induced nausea and vomiting (CINV) is not fully elucidated. We hypothesized that serum iron levels may be associated with CINV because symptoms of iron poisoning resemble the adverse effects of chemotherapy. METHODS: Patients with lung cancer undergoing chemotherapy were included in this retrospective study where serum iron level, unsaturated iron-binding capacity (UIBC), total iron-binding capacity, and ferritin were available prior to and on days 2 and 8 of chemotherapy. RESULTS: Fifty-two patients were analyzed. Iron levels on day 2 were markedly increased in patients receiving highly emetogenic chemotherapy (HEC, 231.0 ± 45.0 µg/dl) and moderately emetogenic chemotherapy (MEC, 226.6 ± 44.2 µg/dl), and mildly increased in patients receiving low emetogenic chemotherapy (LEC, 104 ± 51.4 µg/dl). Significant differences in iron levels on day 2 were observed between the HEC and LEC (P = 0.002) and MEC and LEC (P = 0.0007) groups. UIBC levels decreased on day 2 (18.0 ± 17.5 µg/dl in HEC, 20.4 ± 46.8 µg/dl in MEC, and 123.9 ± 65.9 µg/dl in LEC). There were significant differences in UIBC on days 2 between the HEC and LEC (P = 0.0005) and MEC and LEC (P = 0.0015) groups. No significant changes in these parameters were observed in a minimal risk group. CONCLUSIONS: Iron levels increased according to the emetogenic risk. Accompanied by a markedly increased iron level, non-transferrin bound iron, a highly cytotoxic form of iron, may be present in the serum. Iron removal with an iron-chelating agent may represent a novel antiemetic therapy in patients undergoing chemotherapy.

Asunto(s)

RESUMEN

Objective:To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs.Methods:Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of FeResults:FeConclusions:Fe

RESUMEN

Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of Guinea pigs. Methods: Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of Fe

RESUMEN

For individuals who work outdoors in the winter or play winter sports, chemical hand warmers are becoming increasingly more commonplace because of their convenience and effectiveness. A 32-year-old woman with a history of chronic pain and bipolar disorder presented to the emergency department complaining of a "warm sensation" in her mouth and epigastrium after reportedly ingesting the partial contents of a chemical hand warmer packet containing between 5 and 8 g of elemental iron. She had been complaining of abdominal pain for approximately 1 month and was prescribed unknown antibiotics the previous day. The patient denied ingestion of any other product or medication other than what was prescribed. A serum iron level obtained approximately 6 hours after ingestion measured 235 micrograms/dL (reference range 40-180 micrograms/dL). As the patient demonstrated no new abdominal complaints and no evidence of systemic iron toxicity, she was discharged uneventfully after education. However, the potential for significant iron toxicity exists depending on the extent of exposure to this or similar products. Treatment for severe iron toxicity may include fluid resuscitation, whole bowel irrigation, and iron chelation therapy with deferoxamine. Physicians should become aware of the toxicity associated with ingestion of commercially available hand warmers. Consultation with a medical toxicologist is recommended.

Asunto(s)

RESUMEN

Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2+)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2+) 100-1000µM. The contractile response to Ca(2+) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2+) whereas O2(-) was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2+) influx were impaired only by Fe(2+) 1000µM, and antioxidants had no effect. In skinned fibers, Fe(2+) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2+) sensitivity. These effects are mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000µM, Fe(2+) appears to depress force also by reducing Ca(2+) influx, probably due to a competition at Ca(2+) channels.

Asunto(s)

RESUMEN

Los pacientes intoxicados representan un reto en el enfoque diagnóstico y terapéutico en los serviciosde urgencias. La intoxicación por hierro es una condición médica relativamente frecuente en los pacientes pediátricos y gestantes, dada la fácil adquisición de este mineral en los suplementosvitamínicos, que son corrientemente formulados en las consultas médicas de promoción y prevención y en los programas de control prenatal. La intoxicación aguda por hierro representa un alto potencialletal y para llegar a dicho estado se requieren dosis extremadamente altas como 200 a 250 mg/kg de hierro elemental, aunque recientemente se describe con valores mayores de 150 mg/kg y otros con 75 mg/kg; sin embargo, se empiezan a observar manifestaciones de toxicidad con ingestas mayores de 15 a 20 mg/kg. En el presente artículo se hace una revisión de la intoxicación aguda por hierro desde su metabolismo básico, pasando por los mecanismos existentes para la regulación de las sobrecargasférricas agudas y tomando conceptos necesarios para la comprensión de los procesos fisiopatológicosde las manifestaciones de toxicidad, según el órgano blanco potencialmente lesionado. Se hace una reseña de las modalidades diagnósticas y terapéuticas establecidas, así como los aportes de algunas investigaciones para la posible identificación de antídotos distintos a la deferoxamina. Por último, sepresenta un algoritmo diagnóstico y terapéutico en base a la revisión hecha.

Poisoned patients represent a challenge at the diagnostic and therapeutic approach in theemergency department. Iron poisoning is a relativelycommon medical condition in pregnantand pediatric patients due the easy acquisition of the mineral in supplements often prescribedin medical consultations and prenatal care programs. This poisoning has a high lethal potential,however to reach that state are required extremely high doses as 200 to 250 mg/kg of elementaliron, but recently it´s describe doses of 150 mg/kg and some authors reports of 75 mg/Kg,but are beginning to show signs of toxicity with intakes of 15 - 20 mg/kg. In this paper, we madea review of acute iron poisoning, from basic metabolism, through existing mechanisms for theregulation of acute iron overload and taking concepts for understanding the pathophysiologicalprocesses. This review provides an overview of established diagnostic and therapeutic modalities,as well as input from some research forthe possible identification of various antidotes different to deferoxamine. Finally, it presents a diagnostic and therapeutic algorithm based on the review done.

Asunto(s)