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Importance: Hemochromatosis is rare in domestic animals, and iron-induced myopathy has not been reported in veterinary medicine. This case is the first report of iron-overload myopathy owing to hemochromatosis in a dog., Case Presentation: A 9-year-old spayed female Donggyeong dog presented with severe forelimb lameness. Necropsy revealed an enlarged liver and hemorrhagic lesions in the forelimb muscle. Microscopy showed iron components accumulation in multiple organs, including the liver, forelimb skeletal muscle, spleen, lymph node, and kidney. Prussian blue staining identified iron deposits in both macrophages and parenchymal cells, indicating that the iron accumulation was acquired rather than hereditary. Furthermore, iron components were observed within muscle fibers, accompanied by severe atrophy and myositis., Conclusions and Relevance: Severe necrosis and mild fibrosis were observed in the liver and forelimb skeletal muscles. Based on histological analysis, we diagnosed iron overload myopathy by secondary hemochromatosis. Secondary hemochromatosis with severe muscle atrophy and myositis is very rare, and this is the first report of iron-overload myopathy in a dog., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Korean Society of Veterinary Science.)

The current treatments applied in aquaculture to limit disease dissemination are mostly based on the use of antibiotics, either as prophylactic or therapeutic agents, with vaccines being available for a limited number of fish species and pathogens. Antimicrobial peptides are considered as promising novel substances to be used in aquaculture, due to their antimicrobial and immunomodulatory activities. Hepcidin, the major iron metabolism regulator, is found as a single gene in most mammals, but in certain fish species, including the European sea bass ( Dicentrarchus labrax ), two different hepcidin types are found, with specialized roles: the single type 1 hepcidin is involved in iron homeostasis trough the regulation of ferroportin, the only known iron exporter; and the various type 2 hepcidins present antimicrobial activity against a number of different pathogens. In this study, we tested the administration of sea bass derived hepcidins in models of infection and iron overload. Administration with hamp2 substantially reduced fish mortalities and bacterial loads, presenting itself as a viable alternative to the use of antibiotics. On the other hand, hamp1 seems to attenuate the effects of iron overload. Further studies are necessary to test the potential protective effects of hamp2 against other pathogens, as well as to understand how hamp2 stimulate the inflammatory responses, leading to an increased fish survival upon infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barroso, Carvalho, Nunes, Gonçalves, Rodrigues and Neves.)

Background: Hyperinsulinemia associated with equine metabolic syndrome and pituitary pars intermedia dysfunction is a risk factor for laminitis. Research in other species has shown elevated body iron levels as both a predictor and consequence of insulin resistance. In humans, this is known as dysmetabolic hyperferritinemia., Aim: To explore the relationship between equine hyperinsulinemia and body iron levels., Methods: We reviewed case histories and laboratory results from an open access database maintained by the Equine Cushing's and Insulin Resistance Group Inc. (ECIR). We identified 33 horses with confirmed hyperinsulinemia and laboratory results for serum iron, total iron binding capacity, and ferritin. Pearson correlation was used to test the relationship between insulin and iron indices. Additionally, we performed a secondary analysis of a previously reported controlled trial that was originally designed to test the correlation between iron status and the insulin response in horses. Here, we used a t -test to compare the mean values of insulin and ferritin between horses we categorized as normal or hyperinsulinemic based on their response to an oral challenge., Results: Serum ferritin exceeded published reference range in 100% of the horses identified from the ECIR database. There were no statistically significant associations between insulin indices (RISQI, log insulin) and iron indices (log serum iron, log TSI%, log ferritin). There were trends for a negative association between RISQI and log iron [ r (31) = -0.33, p = 0.058] and a positive association between age and ferritin [ r (30) = 0.34, p = 0.054]. From the secondary data analysis of published data, we found significantly elevated ferritin ( p = 0.05) in horses considered hyperinsulinemic by dynamic insulin testing compared to horses with a normal response., Conclusion: These results suggest the potential for iron overload in hyperinsulinemic horses, a feature documented in other species and should stimulate further study into the relationship between insulin and iron dysregulation in the horse.

Background: Iron oversupplementation in healthy term infants may adversely affect growth and cognitive development., Objective: We hypothesized that early-life iron excess causes systemic and central nervous system iron overload, and compromises social behavior., Methods: The nursing pig was used as a translational model in a completely randomized study. On postnatal day (PD) 1, 24 pigs (1.57 ± 0.28 kg mean ± standard deviation body wt) were assigned to the following treatment groups: 1) nonsupplemented iron-deficient group (NON); 2) control group (CON), intramuscularly injected with iron dextran (100 mg Fe) on PD2; 3) moderate iron group (MOD), orally administered ferrous sulfate at 10 mg Fe · kg body wt-1 · d-1; and 4) high iron group (HIG), orally administered ferrous sulfate at 50 mg Fe · kg-1 · d-1. Piglets were nursed by sows during the study from PD1 to PD21. Tissue iron was analyzed by atomic absorption spectrophotometry. Messenger RNA and protein expression of iron regulator and transporters were analyzed by quantitative reverse transcriptase-polymerase chain reaction and Western blot. A sociability test was performed on PD19-20., Results: Both MOD and HIG treatments (5.51 and 9.85 µmol/g tissue), but not CON (0.54 µmol/g), increased hepatic iron as compared with NON (0.25 µmol/g, P < 0.05). Similarly, the hippocampal iron concentrations in the MOD and HIG groups were 14.9% and 31.8% higher than that of NON, respectively (P < 0.05). In comparison with NON, MOD and HIG treatment repressed DMT1 in duodenal mucosa by 4- and 46-fold, respectively (P < 0.05); HIG drastically induced HAMP in liver by 540-fold (P < 0.05); iron-supplemented groups reduced TFRC in the hippocampus by <1-fold (P < 0.05). However, duodenal expression of ferroportin, the predominant transporter in basal membrane, was not affected by treatment. Despite normal sociability, the MOD and HIG pigs displayed deficits in social novelty recognition (P = 0.004)., Conclusions: Duodenal ferroportin was hyporesponsive to iron excess (MOD and HIG), which caused hippocampal iron overload and impaired social novelty recognition in nursing pigs., (© 2019 American Society for Nutrition.)

Iron though an essential cofactor for many proteins including haemoglobin and cytochromes, when in excess (>1 ppm in water and 100 ppm in fish tissue) elicits toxicity via Fenton reaction inducing oxidative stress. The present study aimed to evaluate the efficacy of dietary Spirulina (Arthrospira platensis) supplementation on waterborne-iron induced oxidative stress in the tissues of Notopterus notopterus. Juvenile fishes were divided randomly into 4 groups, namely, Group-I: control fed with commercial diet only, Group-II, III and IV treated with 0.75 ppm FeCl 3 where Group-II fed with commercial diet only, Group-III with 10% (w/w) Spirulina supplemented commercial diet and Group-IV with 100% (w/w) Spirulina diet only; for 7 and 28 days (n = 6 per group). Tissue oxidative stress biomarkers like lipid peroxidation (LPx), protein carbonylation (PC) and protein thionylation (protein and nonprotein-SH content); antioxidant defence (superoxide dismutase: SOD; catalase; CAT; glutathione peroxidase/reductase: GPx/GR; glutathione s-transferase: GST; metalothionine: MT and reduced glutathione: GSH) and iron accumulation in the gill, liver and muscles tissue were analysed. The augmented oxidative predominance in the tissues with respect to LPx and PC along with decline in antioxidant defence (SOD, CAT, GPx, GR, GST, MT, PSH, NPSH and GSH) by iron was neutralized by Spirulina supplementation in the diet in a dose and duration dependent manner where 100% Spirulina diet for 28 days completely ameliorated iron-induced oxidative stress in fish tissues. Thus, Spirulina can be used as a dietary supplement for fishes cultured in water bodies with iron overload., (Copyright © 2018. Published by Elsevier B.V.)

Case Description: 3 hornbills (2 Papua hornbills [Aceros plicatus] and 1 longtailed hornbill [Tockus albocristatus]) were evaluated because of general listlessness and loss of feather glossiness., Clinical Findings: Because hepatic iron storage disease was suspected, liver biopsy was performed and formalin-fixed liver samples were submitted for histologic examination and quantitative image analysis (QIA). Additional frozen liver samples were submitted for chemical analysis. Birds also underwent magnetic resonance imaging (MRI) under general anesthesia for noninvasive measurement of liver iron content. Serum biochemical analysis and analysis of feed were also performed. Results of diagnostic testing indicated that all 3 hornbills were affected with hepatic iron storage disease., Treatment and Outcome: The iron chelator deferiprone was administered (75 mg/kg [34.1 mg/lb], PO, once daily for 90 days). During the treatment period, liver biopsy samples were obtained at regular intervals for QIA and chemical analysis of the liver iron content and follow-up MRI was performed. In all 3 hornbills, a rapid and large decrease in liver iron content was observed. All 3 methods for quantifying the liver iron content were able to verify the decrease in liver iron content., Clinical Relevance: Orally administered deferiprone was found to effectively reduce the liver iron content in these 3 hornbills with iron storage disease. All 3 methods used to monitor the liver iron content (QIA, chemical analysis of liver biopsy samples, and MRI) had similar results, indicating that all of these methods should be considered for the diagnosis of iron storage disease and monitoring of liver iron content during treatment.

Case Description: 3 adult (24- to 43-year-old) Atlantic bottlenose dolphins (Tursiops truncatus) with chronic episodic malaise and inappetence associated with high serum aminotransferase (alanine aminotransferase and aspartate aminotransferase) activities, high serum iron concentration, and serum transferrin saturation > 80% were evaluated., Clinical Findings: Results of histologic examination of liver biopsy specimens revealed hemosiderosis in all 3 dolphins. Except for chronic lymphocytosis in 1 dolphin, results of extensive diagnostic testing revealed no other abnormalities. For each dolphin, a diagnosis of iron overload of unknown origin was made., Treatment and Outcome: Phlebotomy treatment was implemented to reduce body stores of iron. Each phlebotomy procedure removed 7% to 17% (1 to 3 L) of estimated blood volume. Treatment consisted of an induction phase of weekly phlebotomy procedures for 22 to 30 weeks, which was complete when serum iron concentration and aminotransferase activities were within reference ranges and serum transferrin saturation was < or = 20% or Hct was < or = 30%. Total amount of iron removed from each dolphin was 53 to 111 mg/kg (24.1 to 50.5 mg/lb) of body weight. One dolphin required maintenance procedures at 8- to 12-week intervals when high serum iron concentration was detected., Clinical Relevance: Although the cause of the iron overload and high serum aminotransferase activities remained unknown, phlebotomy treatment successfully resolved the clinicopathologic abnormalities, supporting a role of iron overload in the hepatopathy of the 3 dolphins.

Hepcidin, an antimicrobial and iron-regulating peptide, is a key molecule of the innate immune system of bony fish. In this study, four isoforms of hepcidin genes were characterized from a marine Perciform fish, rockbream (Oplegnathus fasciatus), and the transcriptional modulations of these isoforms in response to different biological stimulations were also examined. All rockbream hepcidin isoform genes exhibited a tripartite structure and their promoter regions displayed typical binding motifs for the transcription factors including C/EBP, HNF, AP, NF-kbeta, GATA, USF and/or STAT. Hepcidin transcripts in juvenile or fingerling tissues were dramatically induced during experimental challenges with various bacterial species, iron overload and rockbream iridovirus infection. The transcription ofhepcidins was regulated in an isoform- and tissue-specific fashion. In addition, we identified for the first time that partially processed hepcidin transcripts were significantly elevated during bacterial infection and iron overload. Results from this study provide a good basis to better understand the isoform-specific role of hepcidin in the fish innate immune system.

Deferiprone is a bidentate oral iron chelator used for the treatment of iron overload in people. The purpose of this study was to determine the pharmacokinetic disposition of deferiprone in the domestic pigeon (Columba livia) and to compare the results with a previous study in the white leghorn chicken. Deferiprone (DFP) was administered orally as a suspension at a single dose of 50 mg/kg to 10 iron-loaded (IL-DFP) pigeons and 10 non--iron-loaded controls (NIL-DFP). Six NIL-DFP birds were also administered deferiprone intravenously to determine the bioavailability of the drug after a 30-day washout period. To evaluate if deferiprone induces its own metabolism, the pharmacokinetic disposition of the drug was also studied in the IL-DFP group after oral therapy with deferiprone at a dosage of 50 mg/kg q12h for 30 days. For each phase, collected blood was analyzed for deferiprone by high-performance liquid chromatography to develop a plasma concentration versus time curve. Deferiprone was rapidly absorbed from the gastrointestinal tract, with plasma concentrations effective for iron chelation maintained for at least 8 hours after administration in iron-loaded birds. The half-life (mean +/- SD) for deferiprone given orally to the IL-DFP and NIL-DFP groups was 2.98 +/- 0.85 hours and 3.26 +/- 1.25 hours, respectively, and when intravenously administered was 3.79 +/- 1.23 hours. The half-life after 30 days of treatment was 3.42 +/- 1.18 hours. Oral bioavailability was 44%. This study demonstrated that oral absorption of deferiprone is acceptable, it does not induce its own metabolism, and the drug was widely distributed in the pigeon, as it was in the chicken, with a longer half-life than that reported in mammals. Minor interspecies variations in the pharmacokinetics of deferiprone exist between chickens and pigeons.

Deferiprone is a bidentate oral iron chelator used for the treatment of transfusional iron overload in people. The purpose of this study was to determine the pharmacokinetic disposition of deferiprone in the white leghorn chicken as a potential model upon which to base therapeutic regimens for the treatment of iron storage disease (hemochromatosis) in affected avian species. A suspension of deferiprone (DFP) was administered orally at a single dose of 50 mg/kg to 10 birds that were iron-loaded (IL-DFP) and 10 non--iron-loaded control birds (NIL-DFP). After a 30-day washout period, 5 birds from the NIL-DFP group were used for a bioavailability study of deferiprone administered intravenously at the same dose. Blood samples were collected at varying intervals over a 24-hour period and were analyzed for deferiprone by high-performance liquid chromatography, then plasma concentration versus time curves were developed. Deferiprone was rapidly absorbed from the gastrointestinal tract of the chicken, with plasma concentrations effective for iron chelation in humans (>20 micromol/L) maintained for at least 8 hours after oral dosing. The half-life (mean +/- SD) of the orally administered deferiprone in the IL-DFP and NIL-DFP groups was 2.91 +/- 0.78 hours and 3.61 +/- 0.90 hours, respectively, and was 2.42 +/- 0.24 hours for deferiprone administered intravenously. The mean oral bioavailability was 93%. Deferiprone is well absorbed and widely distributed in the chicken, with a longer half-life than reported in mammals.

Two-year-old whitefish (Coregonus lavaretus) were exposed for 30 days to episodic iron overload in iron-rich humic water (5%) supplemented with inorganic iron (5 mg FeL(-1)). Two parallel laboratory exposures were performed, one under conditions simulating winter and the other under conditions simulating spring. After exposure, some of the fish were subjected to acute handling stress in the form of a short air challenge to reveal possible modification of the primary and secondary stress responses. In whitefish sampled without additional handling, iron accumulated in the liver (under spring conditions) and gills (under winter and spring conditions); plasma catecholamine and beta-estradiol (both winter and spring groups) as well as blood hematocrit (winter group only) levels were depressed; blood glucose (winter group only) and red blood cell (RBC) Na+ levels (spring group only) were increased. In handled whitefish, liver glycogen phosphorylase (GPase), RBC, and blood glucose stress responses were impaired by the applied exposure conditions, which reflected natural iron-rich humic water. Exposure also removed some physiological effects of the applied ambient conditions: plasma catecholamines and beta-estradiol, gill Na+/K+ -ATPase, and RBC K+ concentration were not different in two iron-exposed fish groups, whereas there was a difference in reference fish. Thus, the physiological effects of this type of subchronic exposure, together with alterations in the acute stress response, can lead to incorrect conclusions being drawn from the results, if the effects of time-dependent stress response are ignored. In conclusion, waterborne iron overload may impair the optimal capacity of whitefish to carry out their normal physiological functions such as responding to external threats.

The clinical use of oral Fe chelators for the treatment of Fe-storage disease in birds requires evaluation. In this study, the efficacy of the Fe chelator deferiprone in reducing hepatic Fe stores, its effects on hematologic, biochemical, and plasma Fe parameters, and its potential toxicity during a 30-day treatment period were investigated in a controlled setting using two model species, the white leghorn chicken (Gallus gallus f. domestica) and the domestic pigeon (Columba livia). A second phase of the study investigated deferiprone-related Fe elimination in the excreta. Deferiprone, administered orally at a dosage of 50 mg/kg twice daily to birds that had been experimentally Fe loaded, significantly reduced hepatic Fe concentrations compared with levels in Fe-loaded and non-Fe-loaded controls. There were no significant alterations in routine clinical hematologic or biochemical parameters, although decreased transferrin saturation was noted in both species. Side effects associated with deferiprone administration were decreased weight gain and significant decreases in plasma Zn concentrations. No mortalities occurred in the pigeons, but there were three deaths in the deferiprone-treated group of Fe-loaded chickens, most likely associated with acute reduction of Fe required for normal enzymatic processes. Histologic changes associated with deferiprone treatment were not noted. Deferiprone caused a dose-dependent increase of Fe in the excreta at oral dosages of 50 and 75 mg/kg once daily in both species. Deferiprone is a promising, orally active Fe chelator for the treatment of Fe overload in birds, although its potential side effects need to be considered.

Iron overload is a very frequent finding in several animal species and a genetic predisposition is suggested. In one of the most commonly reported species with susceptibility for iron overload (mynah bird), it was recently shown that the cause of this pathophysiology is high uptake and retention of dietary iron. Here we compare susceptible (mynahs) with non-susceptible avian species (chickens) by evaluating iron uptake at the intestinal absorptive cell level. Enterocytes from mynahs and chickens were isolated and uptake of Fe(II) and Fe(III) was studied in vitro. It was found that Fe(III) uptake is much lower than Fe(II) uptake for both species. Although liver iron, present only in hepatocytes, was at least 10-fold higher in mynahs than chickens, enterocyte Fe(II) uptake was considerably higher in mynahs. Fe(II) uptake showed saturation at the studied concentrations in both species. Kinetic studies revealed a three-fold increase in Vmax for mynahs. Calculated values for the uptake kinetics of the probable membrane transporter suggest that mynah bird enterocytes have a significantly higher limiting uptake rate, due to the possible increase in the number of transporters when compared with chicken enterocytes. The susceptibility of this species is due to intestinal iron uptake despite hepatic iron accumulation, implicating a 'mis-sensing' of body iron similarly to human hereditary haemochromatosis.

Objective: To investigate the possibility that excessive maternal iron (overload) may contribute to development of congenital leukoencephalomalacia in captive black rhinoceroses., Sample Population: Tissue specimens and serum samples from 18 rhinoceroses in 2 kindreds harboring 4 (possibly 5) affected female calves., Procedure: Fresh and archival sera and necropsy tissue specimens were evaluated to determine the nature and extent of iron overload in captive and wild black rhinoceroses as well as other rhinoceros species., Results: Quantitative serum and tissue assays of iron and iron analytes, corroborated by histopathologic findings, indicated that these kindreds carried the greatest body burdens of iron yet found among captive black rhinoceroses. Fourteen of 18 rhinoceroses had the highest serum ferritin concentrations measured among 64 black rhinoceroses in captivity in the United States. Dams of affected calves had serum ferritin concentrations 2 orders of magnitude higher than clinically normal humans, equids, or free-ranging rhinoceroses. A neonatal serum sample from 1 affected female calf had a high ferritin concentration (approx 100-fold increase), but a male sibling of another affected female did not, suggesting a possible sex disparity in fetal response to maternal iron overload. Morphologic hallmarks of hemochromatosis were prominent in dams and grandams of affected calves., Conclusions and Clinical Relevance: Excessive maternal iron may affect female fetuses more than males, possibly inducing leukoencephalomalacia by catalyzing production of highly toxic hydroxyl free radicals during crucial periods of in utero development. Reduction of maternal iron overload may decrease the probability of developing leukoencephalomalacia and some other disorders commonly affecting rhinoceroses in captivity.