Non-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease.

The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.

Evidence of chronic cadmium exposure identified in the critically endangered Christmas Island flying-fox (Pteropus natalis).

The Christmas Island flying-fox (Pteropus natalis) is the last native mammal on Christmas Island and its population is in decline. Phosphate mining occurs across much of the eastern side of Christmas Island. The phosphate deposits are naturally rich in cadmium, and potentially other metals, which may be threatening the Christmas Island flying-fox population. To test this, concentrations of metals (cadmium, copper, iron, mercury, lead, and zinc) were measured in fur and urine collected from Christmas Island flying-foxes and interpreted concurrently with urinalysis and serum biochemistry data. In addition, metal concentrations in liver and kidney samples from two Christmas Island flying-foxes and associated histological findings from one of these individuals are reported. Fur cadmium concentrations were significantly higher in the Christmas Island flying-fox compared to concentrations found in flying-foxes in mainland Australia. Additionally, 30% of Christmas Island flying-foxes had urine cadmium concentrations exceeding maximum concentrations previously reported in flying-foxes in mainland Australia. Glucosuria and proteinuria were identified in two Christmas Island flying-foxes, suggestive of renal dysfunction. In one aged flying-fox, kidney cadmium concentrations were four-fold higher than toxic thresholds reported for domestic mammals. Microscopic evaluation of this individual identified bone lesions consistent with those described in laboratory animals with chronic cadmium poisoning. These results suggest that Christmas Island flying-foxes are being exposed to cadmium and identification of these sources is recommended as a focus of future research. Unexpectedly, urine iron concentrations in Christmas Island flying-foxes were higher compared to previous studies of Australian mainland flying-foxes, which suggests that urinary excretion of iron may be an important aspect of iron homeostasis in this species whose diet is iron rich.

Investigation into the utility of flying foxes as bioindicators for environmental metal pollution reveals evidence of diminished lead but significant cadmium exposure.

Due to their large range across diverse habitats, flying-foxes are potential bioindicator species for environmental metal exposure. To test this hypothesis, blood spots, urine, fur, liver and kidney samples were collected from grey-headed flying-foxes (Pteropus poliocephalus) and black flying-foxes (P. alecto) from the Sydney basin, Australia. Concentrations of arsenic, cadmium, copper, lead, mercury and zinc and 11 other trace metals were determined using inductively coupled plasma mass spectrometry. As predicted, kidney and fur lead concentrations were lower compared to concentrations found in flying-foxes in the early 1990's, due to reduced environmental lead emissions. Tissue cadmium concentrations in flying-foxes were higher compared to previous studies of flying-foxes and other bat species, suggesting that flying-foxes were exposed to unrecognized cadmium sources. Identification of these sources should be a focus of future research. Urine concentrations of arsenic, cadmium, mercury, and lead were proportional to kidney concentrations. Given that urine can be collected from flying-foxes without handling, this demonstrates that many flying-foxes can be assessed for metal exposure with relative ease. The analysis of blood spots was not viable because of variable metal concentrations in the filter paper used. Fur concentrations of metals correlated poorly with tissue concentrations at the low levels of metals found in this study, but fur could still be a useful sample if flying-foxes are exposed to high levels of metals. Lastly, heat inactivation had minimal impact on metal concentrations in kidney and liver samples and should be considered as a tool to protect personnel working with biohazardous samples.

Limited penetration of cobalt and chromium ions into the cerebrospinal fluid following metal on metal arthroplasty: a cross-sectional analysis.

Background: The purpose of this study was to determine the concentration of cobalt (Co) and chromium (Cr) ions in synovial fluid, blood plasma and cerebrospinal fluid (CSF) of patients with metal-on-metal (MoM) implants, and to assess the relationship between implant history and patient characteristics with ion concentrations in CSF.Methods: An observational, non-randomised cross-sectional study was conducted with patients presenting to a single surgeon for treatment of degenerative conditions of the hip and knee. Blood and fluid samples were collected intraoperatively and analysed for proteins and trace elements.Results: Overall, the presence of an implant was associated with significantly higher Co and Cr concentrations in plasma (controls 5-115 nmol/L Co, 5-232 nmol/L Cr; well-functioning implant recipients 5-469 nmol/L Co, 5-608 nmol/L Cr; hip revisions 6-546 nmol/L Co, 5-573 nmol/L Cr), and for Cr concentrations in CSF (controls 5-24 nmol/L; well-functioning implant recipients 6-36 nmol/L, hip revisions 7-32 nmol/L). In absolute terms, <1% of the levels observed in the joint fluid and <15% of plasma metals appeared in the CSF. Multivariable regression models suggested different transfer mechanisms of Co and Cr to the CSF, with the presence of an implant not associated with ion levels.Conclusion: The presence of MoM implants is associated with significantly higher plasma levels of Co and Cr but not CSF levels, and the CSF/plasma ratio appears to be influenced by the plasma concentration in a nonlinear fashion. Co and Cr may be transferred to the CSF by different mechanisms, and their concentrations appears dependent on other factors yet to be identified. Although higher levels of plasma ions are associated with above average CSF metal concentrations, the thresholds for neurotoxicity remain unclear and require further study.

Genetic effects on toxic and essential elements in humans: arsenic, cadmium, copper, lead, mercury, selenium, and zinc in erythrocytes.

BACKGROUND AND OBJECTIVES: An excess of toxic trace elements or a deficiency of essential ones has been implicated in many common diseases or public health problems, but little is known about causes of variation between people living within similar environments. We estimated effects of personal and socioeconomic characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested for genetic effects using data from twin pairs. METHODS: We used blood samples from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30-92 years of age) and determined element concentrations in erythrocytes by inductively coupled plasma-mass spectrometry. We assessed associations between element concentrations and personal and socioeconomic characteristics, as well as the sources of genetic and environmental variation and covariation in element concentrations. We evaluated the chromosomal locations of genes affecting these characteristics by linkage analysis in 501 dizygotic twin pairs. RESULTS: Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial correlations, concentrations of As and Hg due mainly to common genetic effects. Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters)]}. CONCLUSIONS: Although environmental exposure is a precondition for accumulation of toxic elements, individual characteristics and genetic factors are also important. Identification of the contributory genetic polymorphisms will improve our understanding of trace and toxic element uptake and distribution mechanisms.

Evidence of genetic effects on blood lead concentration.

BACKGROUND: Lead is an environmental pollutant that causes acute and chronic toxicity. Surveys have related mean blood lead concentrations to exogenous sources, including industrial activity, use of lead-based paints, or traffic density. However, there has been little investigation of individual differences in lead absorption, distribution, or toxicity, or of genetic causes of such variation. OBJECTIVES: We assessed the genetic contribution to variation in blood lead concentration in adults and conducted a preliminary search for genes producing such variation. METHODS: Erythrocyte lead concentration was measured by inductively coupled plasma mass spectrometry in venous blood samples from 2,926 Australian adult male and female twins. Mean lead concentrations were compared by place of residence, social class and education, and by the subjects' age, sex, alcohol intake, smoking habits, iron status, and HFE genotype. RESULTS: After adjustment for these covariates, there was strong evidence of genetic effects but not for shared environmental effects persisting into adult life. Linkage analysis showed suggestive evidence (logarithm of odds = 2.63, genome-wide p = 0.170) for a quantitative trait locus affecting blood lead values on chromosome 3 with the linkage peak close to SLC4A7, a gene whose product affects lead transport. CONCLUSIONS: We conclude that genetic variation plays a significant role in determining lead absorption, lead distribution within the body, or both.

Partial correction of sensitivity to oxidant stress in Friedreich ataxia patient fibroblasts by frataxin-encoding adeno-associated virus and lentivirus vectors.

Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of a number of debilitating inherited and acquired neurological conditions. The lack of effective treatments for many such conditions provides a strong rationale for exploring novel therapeutic approaches, including gene therapy. Friedreich ataxia (FRDA), a sensory neuropathy, is a progressive neurodegenerative disease associated with a loss of large sensory neurons from the dorsal root ganglia. Because a mouse model for this well-characterized disease has been generated, we elected to use FRDA as a model disease. In previous studies we achieved efficient and sustained delivery of a reporter gene to PNS sensory neurons, using recombinant adeno-associated viral (AAV) and lentiviral (LV) vectors. In the current study, AAV and LV vectors encoding the human frataxin cDNA were constructed and assessed for frataxin expression and function in primary FRDA patient fibroblast cell lines. FRDA fibroblasts have been shown to exhibit subtle biochemical changes, including increased mitochondrial iron and sensitivity to oxidant stress. Despite the inherent difficulty in working with primary cells, transduction of patient fibroblasts with either vector resulted in the expression of appropriately localized frataxin and partial reversal of phenotype.

Magnesium supplementation does not delay disease onset or increase survival in a mouse model of familial ALS.

Treatment of amyotrophic lateral sclerosis (ALS) with anti-glutamate agents has had some success, but the search continues for more effective glutamate blockers. Magnesium (Mg) ions inhibit the opening of some glutamate receptors, so we increased dietary Mg in a mouse model of ALS in an attempt to modify the course of the disease. From the age of 6 weeks, mutant superoxide dismutase 1 (SOD1) transgenic mice and wild-type controls had either 0, 21.5 or 43 g/l of Mg pidolate added to their drinking water. Disease onset was measured by tests for coordination and forelimb strength, and survival by standard endpoints. Mg levels in the brain were measured in wild-type mice using mass spectrometry. Mutant SOD1 mice on no added Mg became weak at about 105 days, and survived between 114 and 137 days. No difference in either time of onset of weakness, or survival, was seen in mutant SOD1 mice on different doses of Mg. No increase in wild-type brain Mg was found after supplemental Mg. From these results, it appears that a trial of oral Mg supplementation in human ALS is not warranted.