Elsevier

Environmental Research

Volume 111, Issue 8, November 2011, Pages 1124-1136
Environmental Research

Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears

https://doi.org/10.1016/j.envres.2011.08.009Get rights and content

Abstract

We examined biomarkers of selenium status (whole blood Se; serum Se; glutathione peroxidase activity) and thyroid status (concentrations and ratios of thyroxine, T4; tri-iodothyronine, T3; albumin) in polar bears to assess variations among cohorts, and relationships to circulating concentrations of contaminants. Concentrations of total mercury (Hg) in whole blood were similar among cohorts (prime aged males and females, older animals, ages ≥16 years, and young animals, ages 1–5 years; 48.44±35. 81; p=0.253). Concentrations of sum of seven polychlorinated biphenyls (∑PCB7) in whole blood were greater in females (with and without cubs, 26.44±25.82 ng/g ww) and young (26.81±10.67 ng/g ww) compared to males (8.88±5.76 ng/g ww, p<0.001), and significantly related to reduced body condition scores (p<0.001). Concentrations of Se and albumin were significantly greater in males than females (whole blood Se, males, 42.34 pmol/g ww, females, 36.25±6.27 pmol/g ww, p=0.019; albumin, males, 4.34±0.34 g/dl, females, 4.10±0.29 g/dL, p=0.018). Glutathione peroxidase activity ranged from 109.1 to 207.8 mU/mg hemoglobin, but did not differ significantly by sex or age (p>0.08). Thyroid hormones were greater in females (solitary females and females with cubs) compared to males (p<0.001). Biomarkers of Se status and concentrations of T3 were significantly positively related to Hg in all prime aged polar bears (p<0.03). Albumin concentrations were significantly positively related to total TT4, and significantly negatively related to concentrations of ∑PCB7 (p<0.003). Total thyroxine (TT4) was significantly negatively associated with blood concentrations of ∑PCB7 in solitary females (p=0.045). These data suggest that female polar bears were more susceptible to changes in blood-based biomarkers of selenium and thyroid status than males. Further classifications of the physiologic states of polar bears and repeated measures of individuals over time are needed to accurately assess the biological impact of combined toxicant exposures.

Highlights

► Se and TH biomarkers in blood were examined in polar bears. ► Biomarkers were compared to blood concentrations of Hg and ΣPCB7. ► Females were more susceptible to changes in Se and TH status than males. ► Positive and negative associations among biomarkers and contaminants are discussed. ► Further study of the possible adverse biological impact of combined toxicants is warranted.

Introduction

Polar bears (Ursus maritimus) are apex predators of the arctic marine ecosystem and exposed to a combination of inorganic and organic toxicants that bioaccumulate and biomagnify (Atwell et al., 1998, Bentzen et al., 2008, Cardona-Marek et al., 2009, Kucklick et al., 2002). Climate changes may negatively impact the health of polar bears and other arctic marine mammals by altering the transmission of disease agents and exposure to contaminants (Burek et al., 2008, Jenssen, 2006; Letcher et al., 2010). Changes in sea ice are also predicted to reduce feeding opportunities for polar bears and lead to declines in body condition and mass (Derocher et al., 2004). The result of these multiple stressors on polar bear health will likely impact their survival. Correlative analyses have suggested that elevated concentrations of contaminants negatively impact health of polar bears by altering concentrations of hormones, vitamins, and immune status (Bernhoft et al., 2000, Braathen et al., 2004, Skaare et al., 2001). These studies focused on the changes in health biomarkers associated with concentrations of lipophilic contaminants including polychlorinated biphenyls (PCBs), but the possible effects of heavy metals such as mercury (Hg) were not directly examined. The life history characteristics of ursids are known to influence both the concentrations of toxicants and many of the biomarkers assessed (Hellgren et al., 1990; Polischuk et al., 2002; Tomasi et al., 1998). The complicated variations in physiology and biochemistry among cohorts, therefore, require critical assessment before, or in parallel, with the assessment of the role of contaminants on polar bear health.

Biomarkers in toxicology are used to assess the potential responses of biological systems to contaminant exposure. Biomarkers have been categorized as biomarkers of exposure, biomarkers of effect, or biomarkers of susceptibility in comparisons between exposed (or gradients of exposures) and unexposed individuals, cohorts, or populations (Newman, 2010). The lack of unexposed or control (reference) animals in studies of free-ranging species makes these comparisons difficult, and researchers have relied on the use of correlative studies, a weight-of-evidence based approach, clinical diagnostics, or comparisons to threshold effect levels of health risks established for unrelated species (Letcher et al., 2010; Sonne, 2010). The use of biomarkers as indicators of adverse biological impact, however, is complicated by the physiological mechanisms organisms use to maintain homeostasis and optimize metabolic and reproductive activities. For example, polar bears are adapted to the arctic climate by physiological and behavioral modifications such as delayed implantation, seasonal breeding, fasting during maternal denning, and extended periods of lactation (Amstrup, 2003) that are known to be regulated by changes in the concentration of hormones, associated binding proteins, and co-factors (Hellgren, 1998, Norris, 2006; Tomasi et al., 1998). The natural variations of biomarkers due to non-toxicological mechanisms are largely unknown for most free-ranging species. Thus, dealing with confounding variables can be difficult and elusive. Furthermore, cross-sectional studies of free-ranging species cannot control for factors such as the time and dose of contaminants that ultimately led to the changes in the biomarkers assessed and may direct researchers to erroneous conclusions of adverse biological impacts.

Selenium (Se) supports many biological functions and also acts in the protection against toxicosis. Selenium is essential for the formation of many selenocysteine-containing proteins that regulate gonadal maturation, immune function, and the formation of thyroid hormones (Kohrle et al., 2005; Van Lente and Daher, 1992). Selenoproteins are also involved in biological activities in the brain, thyroid, and liver that limit oxidative damage of free radicals induced by aging, pathogens and contaminants (Berry and Ralston, 2008, Khan and Wang, 2010, Mayne, 2003, Ralston and Raymond, 2006, Scandalios, 2005). Selenoproteins reduce oxidative stress through non-enzymatic antioxidant activities that react with oxyradicals directly, and by enzymatic antioxidant activities that catalyze reactions and reduce the number of oxyradicals present. Non-enzymatic antioxidant activities, such as the sequestration of Hg by seleno-compounds, are thought to be the primary mechanism by which marine mammals tolerate high concentrations of dietary Hg (AMAP, 2004a). An equimolar ratio (1:1) between Se and Hg has been suggested in marine organisms to maintain detoxification via sequestration of Hg (Dietz et al., 2000; Woshner et al., 2002; Yoneda and Suzuki, 1997). Selenium binds to mercury in kidney and liver as mercuric selenide (HgSe), an inert end product of the detoxification of methylmercury by demethylation (Wagemann et al., 2000; Woshner et al., 2002; Khan and Wang, 2010), whereas many mercury compounds in circulation are bound to selenoprotein P (Fairweather-Tait et al., 2010). Glutathione peroxidase (GPx) is a Se dependent protein that acts as an enzymatic antioxidant by reduction of potentially damaging hydrogen peroxides (Newman, 2010). Glutathione peroxidase activity has been reported to be altered by the bioaccumulation of Hg, although the exact mechanism is under debate (Brigelius-Flohe, 1999, Carmagnol et al., 1983, Chen et al., 2006).

Thyroid hormones have been used as biomarkers of contaminant exposure as well as the assessment of overall health of marine and terrestrial animals (Rolland, 2000, Rosa et al., 2007; Woshner et al., 2008). The biological actions of thyroid hormones include the regulation of metabolism, growth, cellular differentiation, and reproduction, as well as permissive actions that enable cells to exert an optimal response to other endogenous and exogenous stimuli (Cunningham and Klein, 2007, Norris, 2006). Many factors alter thyroid hormone production including age, sex, reproduction, temperature, diurnal and seasonal cyclicity, and nutrition. Concentrations of PCBs, polybrominated diphenyl ethers (PBDEs), and their metabolites have been associated with alterations in the thyroid hormone levels in polar bears and other species, but these interactions have not been consistent across studies (Braathen et al., 2004, Letcher et al., 2010, Skaare et al., 2001; Sonne, 2010). Heavy metals such as Hg have also been implicated in the disruption of the hypothalamus–pituitary–thyroid (HPT) system (Rolland, 2000), but have not been studied in polar bears. Thyroid status is determined by measuring the concentrations of bound and free fractions of thyroxine (T4) and tri-iodothyronine (T3) that are maintained at optimal levels through negative (and positive) feedback mechanisms to the pituitary (Fig. 1). Disruption of thyroid function can occur through deficiencies in iodine or selenium, changes to the binding proteins in circulation, decreases in the transformation from T4 to T3, or disruption of feedback systems (Bruggeman and Darras, 2009, McNabb, 1995). Baseline data are needed on the selenium and thyroid hormone concentrations of Southern Beaufort Sea (SBS) polar bears to identify variations among cohorts, as well as the possible multiple and interactive effects of toxicants.

In the present study, we question whether blood-based biomarkers of selenium and thyroid status were adequate measures of adverse biological effects of toxicants in polar bears. The biomarkers examined included whole blood and serum concentrations of selenium, glutathione peroxidase activity, thyroid hormone concentrations and ratios, and albumin concentrations. Our first objective was to report the levels of toxicants (Hg and PCBs) and biomarkers in SBS polar bears, describe variations among sex and age cohorts, and compare these to the known values reported in other polar bear sub-populations. The second objective was to examine whether selenium and thyroid status of polar bears was associated with circulating concentrations of Hg and PCB as predicted under the proposed mechanisms of toxicity for these chemicals individually and in combination, with consideration of the physiologic drivers of these biomarkers. These data are presented in the context of key cohorts (e.g., prime reproductive aged males, solitary females in estrous, and females caring for young) and the natural life history of the polar bear.

Section snippets

Sample collection

Animal handling procedures were approved by animal care and use committees at the U.S. Geological Survey Research Program and the University of Alaska Fairbanks (UAF IACUC protocol 04-58). A total of 58 free-ranging SBS polar bears (31 males, 27 females) were captured by immobilization with Telazol (Warner–Lambert)-filled projectile darts fired from a helicopter during spring (March–May) 2007 in collaboration with the U.S. Geological Survey Ursid Research program as described previously (

Concentrations of circulating toxicants

Concentrations of Hg and ∑PCB7 in whole blood (ng/g ww) were positively correlated in males (p<0.001), but unrelated in females (solitary females and females with cubs combined, p=0.834). Concentrations of Hg in whole blood ranged from 10.25 to 228.05 ng/g ww and were similar between cohorts (SEM±SD; solitary females, 69.8±65.2 ng/g ww; females with cubs, 41.6±29.0 ng/g ww; males, 38.2±18.4 ng/g ww; young, 52.4±14.7 ng/g ww; older animals, 63.2±44.9 ng/g ww; ANOVA, f=1.383, p=0.253; Fig. 2A).

Discussion

This study indicated that the concentrations of circulating toxicants differed among the physiologic states of Southern Beaufort Sea (SBS) polar bears. For example, we document that concentrations of Hg and ∑PCB7 were positively correlated in males and solitary females. Concentrations of Hg and ∑PCB7, however, were negatively correlated and more variable among females with cubs. Circulating Hg concentrations can be used as a proxy of recent feeding as Hg compounds are bioavailable to blood

Conclusions

Circulating concentrations of Hg and ∑PCB7 were correlated in male and solitary female polar bears indicating concomitant exposure to heavy metal and lipophilic contaminants. In addition to dietary sources of contaminant exposure, the greater blood ∑PCB7 concentration of animals with low body condition scores suggests that mobilization of lipophilic contaminants from body storage sites to circulation was greater for females than males. Elevations of Se (whole blood and serum concentrations)

Acknowledgments

We thank K. Alexander, S. Amstrup, J.M. Castellini, G. Durner, C. Ebner, C. Kirk, E. Regehr, K. Rode, K. Simac, R. Swor, and G. York for their excellent contributions in the field and laboratory. We are grateful for the contaminant and data analyses provided by B. Anulacion, R. Boyer, J. Bolton, J. Buzitis, R. Pearce, K. Tilbury, and C. Sloan from NOAA Northwest Fisheries Science Center, and for thyroid analyses performed at the Diagnostic Center for Population and Animal Health at Michigan

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    Funding for this project was provided by Grant number 5P20RR016466 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. Laboratory analyses, staff support, and fellowship to K. Knott were provided by the Alaska IDEA Network of Biomedical Research Excellence (INBRE) Program. This research was also supported through a University of Alaska Fairbanks Center for Global Change Student Award funded by the Cooperative Institute for Alaska Research (CIFAR) with funds from the National Oceanic and Atmospheric Administration (NOAA) under cooperative agreement NA08OAR4320751 with the University of Alaska.

    Ethics: animal handling procedures were approved by animal care and use committees at the U.S. Geological Survey Research Program and the University of Alaska Fairbanks (UAF IACUC protocol 04-58).

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