Diagnosis of Disorders of Iron Metabolism in Dogs and Cats.

Iron is an essential element and is used by every cell in the body. This article summarizes iron metabolism and disorders associated with iron metabolism in dogs and cats. The diagnostic tests currently in use for assessing iron status are discussed.

Iron storage disorders in captive wild mammals: the comparative evidence.

Excessive burden of iron, or iron storage disease (ISD), has been reported in a large variety of captive mammal species, including browsing rhinoceroses; tapirs; fruit bats; lemurs; marmosets and some other primates; sugar gliders; hyraxes; some rodents and lagomorphs; dolphins; and some carnivores; including procyonids and pinnipeds. This report collates the comparative evidence for species' susceptibility, recognizing that the data for mammal species are limited. Differences reported in the occurrence of ISD between facilities, or within facilities over periods that span management changes, have been reported in individual cases but are underused in ISD research. Given the species composition, the hypothesis that evolutionary adaptations to the iron content and availability in the natural diet determine a species' susceptibility to ISD (in the face of deviating iron content and availability in diets offered in captivity) seems plausible in many cases. But exceptions, and additional species putatively susceptible based on this rationale, should be investigated. Whereas screening for ISD should be routine in zoo animal necropsy, screening of live individuals may be implemented for valuable species, to decide on therapeutic measures such as chelator application or phlebotomy. Whatever the reasons for ISD susceptibility, reducing dietary iron levels to maintenance requirements of the species in question seems to be a logical, preventive measure.

Iron homeostasis and its disorders in mice and men: potential lessons for rhinos.

During the last decade, there have been remarkable advances in the understanding of iron homeostasis and its disorders. This review summarizes our presentation at the International Workshop on Iron Storage Disease in Black Rhinos that was held in Orlando, Florida, USA, from 23 to 26 February 2011, and it is directed to veterinarians and nutritional experts who treat rhinoceroses. This review summarizes the current knowledge in humans and mice regarding the physiology and molecular basis of iron overload, and it explores how it can be applied to the problem of iron overload in captive rhino populations.

Avian iron storage disease: variations on a common theme?

Many frugivorous avian species kept in captivity develop iron storage disease (ISD) as indicated by high concentrations of hepatic iron and hemosiderin deposits in hepatocytes or phagocytes. In several susceptible species fed diets containing moderate levels of iron, ISD develops because of an inability to match rates of iron absorption to tissue needs. Evidence suggests that the pathophysiologic basis of excess iron absorption is due to high levels of expression of divalent metal transporter-1 that transports iron into enterocytes in the proximal intestine, and ferroportin that exports iron to the circulation. The regulatory basis for this inability to sufficiently down-regulate iron absorption is unknown, but disruptions in the hepcidin-ferroportin axis are likely candidates based on recent research in humans and laboratory rodents. It is likely that ISD-susceptible avian species evolved on foods that were very low in bioavailable iron, so there was strong selection pressure for the efficient capture of the small amount of dietary iron but low selection pressure for preventing iron toxicities. Thus, the transporters and regulatory networks for iron absorption seem to be heavily skewed toward iron storage even when food items that are high in iron are consumed. Infections, trauma and neoplasias that trigger an acute phase response may exacerbate ISD in susceptible species and may be the primary cause in species that are normally resistant to ISD (i.e., those that are normally able to shut down intestinal iron absorption when iron stores are replete). The evolutionary basis that resulted in some avian species to be susceptible to ISD (e.g., dietary cause) seems to differ from many inherited ISD disorders in humans that are thought to have evolved to bolster protection against infectious diseases. However the evolutionary basis of ISD in other mammalian species might be more similar to that in ISD-susceptible avian species.

Browse diversity and iron loading in captive sumatran rhinoceroses (Dicerorhinus sumatrensis): a comparison of sanctuary and zoological populations.

Iron storage disease (ISD) is now recognized as a serious clinical disorder acquired by two species of browsing rhinoceroses, the African black (Diceros bicornis) and the Asian Sumatran (Dicerorhinus sumatrensis) rhinoceroses, when displaced from their natural habitats. The most complete knowledge of ISD comes from studies of the black rhinoceros, but the Asian species is also at risk. Sumatran rhinoceroses housed in traditional zoological settings outside of range countries have suffered significant morbidity and mortality potentially related to ISD induced by diet and/or other confinement conditions. With so few animals in captivity, very little information exists on iron loading in the Sumatran rhinoceros. To better characterize the problem, we retrospectively compared captive management conditions of Sumatran rhinoceroses housed under traditional zoological care with those in two native sanctuary environments. In general, zoo rhinoceroses are offered a paucity of plants and browse species compared with their sanctuary and wild counterparts managed in native rainforest habitats. Iron analyte levels and limited histopathologic observations in these populations suggest variable tendencies to overload iron, dependent upon differences in managed diet and individual food preferences. More detailed investigation of these markedly dissimilar ex situ populations is warranted to better understand the role of nutrition and other conditions affecting iron loading in browser rhinoceroses.

Plant phenolics and their potential role in mitigating iron overload disorder in wild animals.

Phenolic compounds are bioactive chemicals found in all vascular plants but are difficult to characterize and quantify, and comparative analyses on these compounds are challenging due to chemical structure complexity and inconsistent laboratory methodologies employed historically. These chemicals can elicit beneficial or toxic effects in consumers, depending on the compound, dose and the species of the consumer. In particular, plant phenolic compounds such as tannins can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo-managed wild animal species are sensitive to iron overload, and these species tend to be offered diets higher in iron than most of the plant browse consumed by these animals in the wild and in captivity. Furthermore, these animals likely consume diets higher in polyphenols in the wild as compared with in managed settings. Thus, in addition to reducing dietary iron concentrations in captivity, supplementing diets with phenolic compounds capable of safely chelating iron in the intestinal lumen may reduce the incidence of iron overload in these animal species. It is recommended to investigate various sources and types of phenolic compounds for use in diets intended for iron-sensitive species. Candidate compounds should be screened both in vitro and in vivo using model species to reduce the risk of toxicity in target species. In particular, it would be important to assess potential compounds in terms of 1) biological activity including iron-binding capacity, 2) accessibility, 3) palatability, and 4) physiological effects on the consumer, including changes in nutritional and antioxidant statuses.

Management strategies of iron accumulation in a captive population of black rhinoceroses (Diceros bicornis minor).

During routine health screens for black rhinoceroses (Diceros bicornis minor) in a captive setting, serum iron and ferritin were analyzed as well as total iron binding capacity and total iron saturation. Trends for ferritin and percent iron saturation showed steady increases since 2003 in four of four animals (three males; one female) with two animals (one male; one female) consistently showing higher elevations over conspecifics. The historical diet had been comprised of a commercial or in-house complete pelleted feed; several species of fresh browse, Bermuda grass, alfalfa and timothy hays, as well as enrichment and training items (apples, carrots, sweet potatoes, and a small amount of leafy greens and vegetables). In 2009, one of the three male rhinoceroses showed a threefold increase in ferritin and concurrently exhibited clinical signs of lethargy, decreased appetite, and disinterest in training. The lone female showed a twofold increase; she also became reproductively acyclic in the prior year. The male was immobilized for examination and phlebotomy. During the same time period, a new version of the complete pelleted feed, with a reduced amount of iron, was introduced. Subsequent to the diet change, the male's ferritin levels have consistently declined, and the female started cycling again. Even with these corrective steps to reduce iron levels, levels of iron saturation remained high, and ferritin levels were still above 1,500 ng/ml. Therapeutic phlebotomy was instituted via a rigorous training program that allowed phlebotomies over a 30-min time frame. This was possible because of a long-term training program for the animals, consistent training personnel, routine collection of samples on a monthly basis, and general comfort level of the animals in the restraint chute. The results of this integrated approach showed some significant improvements and an overall positive impact on the animals.

Review of laboratory and necropsy evidence for iron storage disease acquired by browser rhinoceroses.

Necropsies of two browser rhinoceroses, African black (Diceros bicornis) and Sumatran (Dicerorhinus sumatrensis), often reveal extensive iron-pigment deposition in various tissues. This condition (hemosiderosis) has not been observed in species that are natural grazers, African white (Ceratotherium simum) and Asian greater one-horned (Indian; Rhinoceros unicornis), nor in any species free ranging in the wild. The causes, clinical significance, and consequences of captivity-acquired hemosiderosis have remained controversial despite two decades of compelling evidence that iron tends to accumulate logarithmically in all members of affected species in proportion to periods of expatriation; total-body iron loads can reach 10-fold in less than 3 yr and eventually exceed reference ranges by two to three orders of magnitude; iron overburdens are accompanied by laboratory and histopathologic evidence of cellular injury, necrosis and other clinical consequences characteristic of chronic pathologic iron storage [corrected] disorders (ISD) in humans and other species (hemochromatosis); and that ISD develops in many other exotic wildlife species displaced from their natural habitats. The historical evolution of evidence establishing the development of pathologic ISD in browser (but not in grazer) rhinoceroses and the possible relevance of ISD to other conditions affecting these two species will be reviewed. Evidence reviewed includes new as well as published data derived from quantitative measurements of iron analytes in sera and necropsy tissues and histopathologic evaluations of current and past necropsies of captive and free-ranging rhinoceroses of all four available species. The evolutionary, husbandry, and conservation implications of ISD in rhinoceroses are relevant to understanding ISD acquired by many other species of exotic wildlife when displaced from their natural environments.

Role of hepcidin in iron metabolism and potential clinical applications.

The relatively recent discovery of hepcidin has stimulated renewed research interest in iron metabolism and iron-related disorders, emphasizing the importance of this hormone in many normal and pathologic processes. Important questions still remain to be answered; however, research to date offers promising diagnostic and therapeutic implications for both humans and veterinary species.

Iron homeostasis and disorders in dogs and cats: a review.

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

Hepatic iron accumulation over time in European starlings (Sturnus vulgaris) fed two levels of iron.

European starlings (Sturnus vulgaris) were used as a passerine bird model to examine the effect of dietary iron on the level of hepatic iron in birds. Nestling and fledgling starlings (n = 56) were raised on a controlled-iron diet. When birds maintained constant body weight, they were assigned in pairs to cages, and baseline sampling was performed. Pairs were then assigned to one of two diets: the controlled-iron diet (168 ppm, dry basis) or a high-iron diet (3,035 ppm, dry basis). Dry-matter intake and iron consumption were recorded. Dry-matter intake did not differ between the dietary treatment groups and was stable during treatment periods. Iron intake was higher in the high-iron group (P < 0.05). Birds were euthanized at baseline, 8 wk, and 16 wk. Body, liver, and spleen weights were measured. Hepatic iron and copper concentrations were determined. Body weight did not differ between the two treatment groups or among individuals for the study duration. Liver iron concentration differed over time and between treatment groups. Birds receiving both treatments had similar liver iron content at week 8 (3,107 +/- 228.6 ppm and 3,122 +/- 306.2 ppm high and controlled iron, respectively; P > 0.05), but by week 16, birds consuming the high-iron diet had greater hepatic iron levels than those consuming the controlled-iron diet (5,929 +/- 937.2 ppm and 3,683 +/- 229.5 ppm high and controlled iron, respectively; P < 0.05). Birds on the controlled-iron diet also had higher hepatic iron at 16 wk than at 8 wk. Liver copper decreased over time in all birds regardless of treatment. Results show that both dietary iron level and duration of time influenced hepatic iron storage. The controlled-iron diets still allowed accumulation of hepatic iron in an 8-wk period.