Fig 2 - uploaded by Hanae Pouillevet
Content may be subject to copyright.
Serum protein electrophoreses showing an example of the serum protein distribution in a black rhinoceros (BR, total proteins 92 g/L, α 2 globulins 27 g/L) and a white rhinoceros (WR, total proteins 75 g/L, α 2 globulins 9.6 g/L). Note the increased size of the α 2 globulin region in the BR compared to the WR (grey areas). https://doi.org/10.1371/journal.pone.0231514.g002
Source publication
Iron Overload Disorder (IOD) is a syndrome developed by captive browsing rhinoceroses like black rhinoceroses (Diceros bicornis), in which hemosiderosis develops in vital organs while free iron accumulates in the body, potentially predisposing to various secondary diseases. Captive grazing species like white rhinoceroses (Ceratotherium simum) do no...
Citations
... 10,25 Captive BR are known to suffer from iron accumulation (iron overload disorder), reduced insulin sensitivity, and increased inflammatory and oxidative stress. [29][30][31]36 One of the challenges of ex situ conservation of rhinoceros is that the food sources in the wild may not match the food sources available in zoos. 6 Finding a suited food source for BR is considerably more difficult than for WR or GOHR. ...
... The fact that iron can reversibly oxidize is the mechanism of its pathophysiology. From one point of view, this tendency is critical for iron metabolic functions; but, also, it could lead to a hazardous process in which dangerous oxidant species like hydroxyl can be generated (Pouillevet et al. 2020). An abnormal hemoglobin level and related biochemical indices were reported in a study on 99 patients with COVID-19. ...
The clinical state of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been considered a pandemic disease (COVID-19) that is rapidly spreading worldwide. Despite all global efforts, the only treatment for COVID-19 is supportive care and there has been no efficient treatment to fight this plague. It is confirmed that patients with chronic diseases such as cardiovascular disorder and diabetes; are more vulnerable to COVID-19. In the severe type of COVID-19, laboratory findings showed a remarkably enhanced C-reactive protein, IL-6 serum, Iron, and ferritin, which suggest an inflammatory response. Inflammation results in iron homeostasis imbalance and causes iron overload, exacerbating the SARSCOV2 infection. More importantly, recent studies have established that SARS-CoV-2 needs iron for viral replication and also activation. As a result, managing iron overload in diabetic patients with COVID-19 could be an early therapeutic approach to limit the lethal inflammatory response of COVID-19. In this review, Deferoxamine (DFO) has been proposed as an effective iron chelator agent.
Graphical Abstract
... 23,33,34,36,76 Serum iron measurement is available on most automated wet chemistry systems, using the spectrophotometric ferrozine zinc method. Decreases in serum iron in animals with inflammatory disease compared with apparently healthy groups were investigated and found to be present in African elephants, white rhidetermination of SAA in cats and horses and CRP in dogs, and validation studies have been published for several of these systems in these species.[77][78][79][80] ...
Applications for acute phase reactants (APRs) in nondomesticated mammals include identifying inflammatory disease, monitoring the course of specific disease processes and recovery during rehabilitation, detecting preclinical or subclinical disease, being used as bioindicators for monitoring population and ecosystem health, and as markers of stress and animal welfare. Serum amyloid A, haptoglobin, C-reactive protein, fibrinogen, albumin, and iron are most commonly measured. The procedure for evaluating an APR in a nondomesticated mammalian species should follow a stepwise approach beginning with an assessment of analytical performance, followed by an evaluation of overlap performance, clinical performance, and impact on patient outcomes and management. The lack of species-specific standards and antibodies for nondomesticated mammals presents a challenge, and more attention needs to be focused on assessing cross-reactivity and ensuring adequate analytical performance of APR assays. Sample selection for the initial evaluation of APRs should consider preanalytical influences and should originate from animals with confirmed inflammatory disease and healthy animals. Reference intervals should be generated according to published guidelines. Further evaluation should focus on assessing the diagnostic utility of APRs in specific disease scenarios relevant to a species. Greater attention should be paid to assay performance and uniformity of methods when using APRs for population and ecosystem surveillance. Veterinary clinical pathologists should work closely with zoo veterinarians and wildlife researchers to optimize the accuracy and utility of APR measurements in these various conservation medicine scenarios.
... Iron overload increases the non-transferrin-bound iron. Unbound iron is particularly hazardous because it readily accepts and donates electrons while switching between the two forms, Fe 2+ and Fe 3+ , leading to free radical generation [38]. Hence, "free iron" is highly reactive and can participate in Fenton's or Haber-Weiss's reactions, generating ROS, such as highly dangerous hydroxyl radicals [39]. ...
Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.
... Furthermore, iron dysregulation can interfere with systemic and local immune function via numerous intricate pathways (Cronin et al., 2019;Mu et al., 2021). Although studies of immune cell function (Roth and Vance, 2007;Vance et al., 2004), gut microbiome (Roth et al., 2019b;Williams et al., 2019) and serum ROS (Paglia et al., 1996;Pouillevet et al., 2020) have revealed differences among rhinoceros species, evidence directly linking body iron load to impaired health is lacking. ...
... Percent transferrin saturation is often considered another useful marker of body iron status, but its usefulness also varies depending on the aetiology of iron loading (Wood, 2014). Furthermore, it has proven technically difficult to measure accurately in rhinoceroses (Pouillevet et al., 2020;personal experience). Potential alternative serum biomarkers include non-transferrin bound iron (NTBI), which has received considerable attention in the human health field (Zhu et al., 2016). ...
... Higher oxidative stress markers in BRs were recently reported in a study that compared BR and WR serum (Pouillevet et al., 2020); however, the ratio of males to females within the two species was 6:9 and 6:18, respectively. A strong sex bias was noted early in Study 1 of this project with male rhinoceros samples exhibiting significantly more ORP on average than female samples, so imbalances were largely corrected during Study 2 to avoid influence from the significant confounding factor of sex in the final interspecies analysis. ...
A consequence of the poaching crisis is that managed rhinoceros populations are increasingly important for species conservation. However, black rhinoceroses (BR; Diceros bicornis) and Sumatran rhinoceroses (SR; Dicerorhinus Sumatrensis) in human care often store excessive iron in organ tissues, a condition termed iron overload disorder (IOD). IOD research is impeded by the challenge of accurately monitoring body iron load in living rhinoceroses. The goals of this study were to (i) determine if labile plasma iron (LPI) is an accurate IOD biomarker and (ii) identify factors associated with iron-independent serum oxidative reduction potential (ORP). Serum (106 samples) from SRs (n = 8), BRs (n = 28), white rhinoceros (n = 24) and greater one-horned rhinoceros (GOH; n = 16) was analysed for LPI. Samples from all four species tested positive for LPI, and a higher proportion of GOH rhinoceros samples were LPI positive compared with those of the other three species (P < 0.05). In SRs, the only LPI-positive samples were those from individuals clinically ill with IOD, but samples from outwardly healthy individuals of the other three species were LPI positive. Serum ORP was lower in SRs compared with that in the other three species (P < 0.001), and iron chelation only reduced ORP in the GOH species (P < 0.01; ∼5%). Serum ORP sex bias was revealed in three species with males exhibiting higher ORP than females (P < 0.001), the exception being the SR in which ORP was low for both sexes. ORP was not associated with age or serum iron concentrations (P ≥ 0.05), but was positively correlated with ferritin (P < 0.01). The disconnect between LPI and IOD was unanticipated, and LPI cannot be recommended as a biomarker of advanced rhino IOD. However, data provide valuable insight into the complex puzzle of rhinoceros IOD.
... The UIBC (unsaturated iron-binding capacity) may also be determined as part of TIBC assessment methods. Recent work noted challenges with a methodology of assaying TIBC in BR involving pH shifts; however, different methods may have more success [70,71]. While there are a wide variety of methods possible for TIBC or transferrin, assessments validate the equivalence of either approach [68,72,73]. ...
... The recent notion that ferritin should be a stand-alone diagnostic and that its value in monitoring IOD should be dismissed remains problematic [70,84,85]. In fact, in veterinary medicine, few diseases utilize a single serum biochemical marker for the diagnosis, let alone progression, of a disease state (e.g., renal disease). ...
... Oxidative damage and inflammation, which is inevitable with elevated iron, has had the attention of many rhinoceros researchers [70,82,92]. While these markers also do not indicate IOD, they can imply the negative effects of IOD and may connect with disease monitoring. ...
Simple Summary: Black rhinoceros under human care are predisposed to Iron Overload Disorder that is unlike the hereditary condition seen in humans. We aim to address the black rhino caretaker community at multiple perspectives (keeper, curator, veterinarian, nutritionist, veterinary technician, and researcher) to describe approaches to Iron Overload Disorder in black rhinos and share learnings. This report includes sections on (1) background on how iron functions in comparative species and how Iron Overload Disorder appears to work in black rhinos, (2) practical recommendations for known diagnostics, (3) a brief review of current investigations on inflammatory and other potential biomarkers, (4) nutrition knowledge and advice as prevention, and (5) an overview of treatment options including information on chelation and details on performing large volume voluntary phlebotomy. The aim is to use evidence to support the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population. Abstract: Critically endangered black rhinoceros (BR) under human care are predisposed to non-hemochromatosis Iron Overload Disorder (IOD). Over the last 30 years, BR have been documented with diseases that have either been induced by or exacerbated by IOD, prompting significant efforts to investigate and address this disorder. IOD is a multi-factorial chronic disease process requiring an evidence-based and integrative long-term approach. While research continues to elucidate the complexities of iron absorption, metabolism, and dysregulation in this species, preventive treatments are recommended and explained herein. The aim of this report is to highlight the accumulated evidence in nutrition, clinical medicine, and behavioral husbandry supporting the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population.
Poaching is again driving rhinos to the brink of extinction due to the demand for rhino horn products consumed for cultural, medicinal, and social purposes. Paradoxically, the same horn for which rhinos are killed may contain valuable clues about the species’ health. Analyses of horn composition could reveal such useful bioindicators while elucidating what people actually ingest when they consume horn derivatives. Our goals were to quantify minerals (including metals) in rhino horn and investigate sampling factors potentially impacting results. Horns (n = 22) obtained during necropsies of white (n = 3) and black (n = 13) zoo rhinos were sampled in several locations yielding 182 specimens for analysis. Initial data exposed environmental (soil) contamination in the horn’s exterior layer, but also confirmed that deep (≥ 1 cm), contaminant-free samples contained measurable concentrations of numerous minerals (n = 18). Of the factors examined in deep samples, color-associated mineral differences were the most profound with dark samples higher in zinc, copper, lead, and barium (p < 0.05). Our data demonstrate that rhino horns contain both essential and potentially toxic minerals that could be relevant to rhino health status, but low concentrations make their human health benefits or risks unlikely following consumption.
The critically endangered black rhinoceros (Diceros bicornis; black rhino) experiences extinction threats from poaching in-situ. The ex-situ population, which serves as a genetic reservoir against impending extinction threats, experiences its own threats to survival related to several disease syndromes not typically observed among their wild counterparts. We performed an untargeted metabolomic analysis of serum from 30 ex-situ housed black rhinos (Eastern black rhino, EBR, n = 14 animals; Southern black rhino, SBR, n = 16 animals) and analyzed differences in metabolite profiles between subspecies, sex, and health status (healthy n = 13 vs. diseased n = 14). Of the 636 metabolites detected, several were differentially (fold change > 1.5; p < 0.05) expressed between EBR vs. SBR (40 metabolites), female vs. male (36 metabolites), and healthy vs. diseased (22 metabolites). Results suggest dysregulation of propanoate, amino acid metabolism, and bile acid biosynthesis in the subspecies and sex comparisons. Assessment of healthy versus diseased rhinos indicates involvement of arachidonic acid metabolism, bile acid biosynthesis, and the pentose phosphate pathway in animals exhibiting inflammatory disease syndromes. This study represents the first systematic characterization of the circulating serum metabolome in the black rhinoceros. Findings further implicate mitochondrial and immune dysfunction as key contributors for the diverse disease syndromes reported in ex-situ managed black rhinos.
Introduction:
Acute phase reactants (APRs) have not been investigated in free-living African elephants (Loxodonta africana), and there is little information about negative APRs albumin and serum iron in elephants.
Objectives:
We aimed to generate reference intervals (RIs) for APRs for free-living African elephants, and to determine the diagnostic performance of APRs in apparently healthy elephants and elephants with inflammatory lesions.
Methods:
Stored serum samples from 49 apparently healthy and 16 injured free-living elephants were used. The following APRs and methods were included: albumin, bromocresol green; haptoglobin, colorimetric assay; serum amyloid A (SAA), multispecies immunoturbidometric assay, and serum iron with ferrozine method. Reference intervals were generated using the nonparametric method. Indices of diagnostic accuracy were determined by receiver-operator characteristic (ROC) curve analysis.
Results:
Reference intervals were: albumin 41-55 g/L, haptoglobin 0.16-3.51 g/L, SAA < 10 mg/L, and serum iron 8.60-16.99 μmol/L. Serum iron and albumin concentrations were lower and haptoglobin and SAA concentrations were higher in the injured group. Serum iron had the best ability to predict health or inflammation, followed by haptoglobin, SAA, and albumin, with the area under the ROC curve ranging from 0.88-0.93.
Conclusions:
SAA concentrations were lower in healthy African vs Asian elephants, and species-specific RIs should be used. Serum iron was determined to be a diagnostically useful negative APR which should be added to APR panels for elephants.
