Pall S. Leifsson

Are organohalogen contaminants a cofactor in the development of renal lesions in East Greenland polar bears (Ursus maritimus)

Tissues of polar bears (Ursus maritimus) from East Greenland contain the highest concentrations of organohalogen contaminants (OHCs) among subpopulations of any mammalian species in the Arctic. Negative associations also have been found between OHC concentrations and bone mineral density and liver histology parameters for this subpopulation of polar bears. The present study examined the OHC concentrations and adverse effects on renal tissue for 75 polar bears collected during 1999 to 2002. Specific lesions were diffuse glomerular capillary wall thickening, mesangial glomerular deposits, tubular epithelial cell hyperplasia, hyalinization of the tubular basement membrane, tubular dilatation, atrophy and necrosis, tubular medullary hyalin casts, interstitial fibrosis, and mononuclear cell infiltration. With the exception of mononuclear cell infiltrations, all these parameters were correlated with age, whereas none was associated with the sex of the animals. In an age-controlled statistical analysis of covariance, increases in glomerular mesangial deposits and interstitial fibrosis were significantly (p < 0.05) correlated with polybrominated diphenyl ether (sigmaPBDE) concentrations in subadults. In adult males, statistically significant (p < 0.05) positive correlations were found for tubular epithelial cell hyperplasia and dieldrin concentration; diffuse glomerular capillary wall thickening and chlordane (sigmaCHL) concentrations, and tubular medullary hyalin casts and sigmaCHL, sigmaPBDE, polychlorinated biphenyl, and hexachlorocyclohexane concentrations. The lesions were consistent with those reported previously in highly OHC-contaminated Baltic seal populations and exposed laboratory animals. The renal lesions were a result of aging. However, based on the above statistical findings as well as the nature of the findings, we suggest that long-term exposure to OHCs may be a cofactor in renal lesion occurrence, although other cofactors, such as exposure to heavy metals and recurrent infections from microorganisms, cannot be ruled out. This is new and important knowledge in the assessment of health status among wildlife populations and humans relying on food resources that are contaminated with OHCs.

Are liver and renal lesions in East Greenland polar bears (Ursus maritimus) associated with high mercury levels

BackgroundIn the Arctic, polar bears (Ursus maritimus) bio-accumulate mercury as they prey on polluted ringed seals (Phoca hispida) and bearded seals (Erignathus barbatus). Studies have shown that polar bears from East Greenland are among the most mercury polluted species in the Arctic. It is unknown whether these levels are toxic to liver and kidney tissue.MethodsWe investigated the histopathological impact from anthropogenic long-range transported mercury on East Greenland polar bear liver (n = 59) and kidney (n = 57) tissues.ResultsLiver mercury levels ranged from 1.1–35.6 μg/g wet weight and renal levels ranged from 1–50 μg/g wet weight, of which 2 liver values and 9 kidney values were above known toxic threshold level of 30 μg/g wet weight in terrestrial mammals. Evaluated from age-correcting ANCOVA analyses, liver mercury levels were significantly higher in individuals with visible Ito cells (p < 0.02) and a similar trend was found for lipid granulomas (p = 0.07). Liver mercury levels were significantly lower in individuals with portal bile duct proliferation/fibrosis (p = 0.007) and a similar trend was found for proximal convoluted tubular hyalinisation in renal tissue (p = 0.07).ConclusionBased on these relationships and the nature of the chronic inflammation we conclude that the lesions were likely a result of recurrent infections and ageing but that long-term exposure to mercury could not be excluded as a co-factor. The information is important as it is likely that tropospheric mercury depletion events will continue to increase the concentrations of this toxic heavy metal in the Sub Arctic and Arctic marine food webs.

Mercury contamination in spotted seatrout, Cynoscion nebulosus: An assessment of liver, kidney, blood, and nervous system health

Marine fishes in South Florida (Florida Keys-Florida Bay-Everglades region) accumulate higher concentrations of mercury (Hg) in their tissues than similar fishes from other areas of the southeastern U.S., though it is not known whether these elevated levels affect fish health. In this study, we used quantifiable pathological and biochemical indicators to explore Hg-associated differences in marine fish from South Florida, where Hg contamination is high, and from Indian River Lagoon, Florida, which served as a reference area. Hg concentrations in all tissues of mature spotted seatrout (Cynoscion nebulosus) from South Florida were significantly higher than those from Indian River Lagoon and were within the threshold range of those in studies where effects of Hg exposure have been observed. The distribution of Hg among tissues followed the same trend in both areas, with the greatest concentration in kidney tissue, followed by liver, muscle, brain, gonad, and red blood cells. Blood-plasma biochemistry showed that concentrations of iron, inorganic phosphate, lactate dehydrogenase, and aspartate aminotransferase were significantly less in South Florida. Also, fructosamine and alkaline phosphatase were significantly less in South Florida. Liver histology revealed that pyknosis/necrosis, interstitial inflammation, and bile duct hyperplasia were found only in seatrout from South Florida, and steatosis/glycogen was more frequently found in Indian River Lagoon specimens. In renal tissue, interstitial inflammation, glomerular dilatation and thickening, and tubular degeneration and necrosis were more frequently found in South Florida specimens. Changes in the liver cytoskeleton and morphology may explain some of the differences in blood parameters between study areas. Neurochemical analyses showed that brain N-methyl-d-aspartic acid (NMDA) receptors (but not those of muscarinic cholinergic receptors, monoamine oxidase, or acetylcholinesterase) were significantly less in fish from South Florida than from Indian River Lagoon. These findings provide compelling evidence that elevated Hg could cause quantifiable pathological and biochemical changes that might influence the health of spotted seatrout and could also affect other marine fish species.

Do organohalogen contaminants contribute to histopathology in liver from East Greenland polar bears (Ursus maritimus)

In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.

Cadmium toxicity to ringed seals (Phoca hispida): an epidemiological study of possible cadmium-induced nephropathy and osteodystrophy in ringed seals (Phoca hispida) from Qaanaaq in Northwest Greenland.

The Greenland marine food chains contain high levels of cadmium, mercury and selenium. Concentrations of cadmium in the kidney of ringed seals (Phoca hispida) from the municipalities of Qaanaaq and Upernavik (Northwest Greenland) are among the highest recorded in the Arctic. The purpose of the study was to determine whether cadmium-induced damage in the kidneys and the skeletal system could be detected among 100 ringed seals from Northwest Greenland. The cadmium concentrations in the kidney cortex ranged from 0 to 248 microg/g wet weight (mean=44.5, N=100) in the 99 kidneys examined. Experience from cadmium-poisoned humans and laboratory mammals indicates that concentrations above 50-200 microg/g wet wt. may induce histopathological changes. Overall, 31 of the ringed seals had cadmium concentrations in the kidney cortex above 50 microg/g wet wt., 11 had concentrations above 100 and one had a concentration above 200 microg/g wet wt. Obvious histopathological changes (categorised mainly as glomerulonephritis) were found in 10 of the seals; however, none of these changes could be attributed to cadmium-induced renal damage (mainly tubulopathy) as described for other species. Damage to the proximal kidney tubules is known to induce demineralisation of the skeletal system (Fanconis syndrome). Therefore, the three lowest lumbar vertebrae were scanned in 91 seals to measure the content of calcium. The 10 cases of nephropathy could neither be linked to the degree of mineralisation of the skeleton nor to the cadmium concentrations. Furthermore, the degree of mineralisation of the skeleton was not correlated with the cadmium concentration, age or sex. It can therefore be concluded that despite high levels of cadmium, none of the ringed seals showed any signs of cadmium-induced nephropathy or osteodystrophy. This might be explained by the composition of the ringed seals diet, which contains high levels of vitamin D, calcium, phosphorus, zinc, selenium and protein. These elements are all likely to counteract cadmium-induced damage. It is speculated that ringed seal are not particularly vulnerable to osteodystrophy, due to their continuous growth (bone mineralisation) throughout life and the oestrogen hormonal activity of females throughout life.

Taenia solium porcine cysticercosis: viability of cysticerci and persistency of antibodies and cysticercal antigens after treatment with oxfendazole.

The aim of this study was to assess the effect of treating Taenia solium infected pigs with oxfendazole (OFZ) on viability and clearance of cysticerci and the corresponding persistence of specific antibody isotypes (IgG(total), IgG1, IgG2 and IgA) and circulating cysticercal antigen (CCA). Antibody isotypes and CCA responses were measured by antibody-ELISA (Ab-ELISA) and antigen ELISA (Ag-ELISA), respectively. Correlations were made between antibodies, CCA and the total number of cysticerci enumerated at necropsy. Forty pigs with cysticercosis were randomly allocated into two groups: Treatment group (n=20) was treated with OFZ at 30 mg/kg orally while the treatment control group (n=20) was not treated. Five uninfected pigs served as negative controls. Pigs were killed at 1, 4, 8 and 26 weeks post-treatment (wkpt). Overall, the mean total cyst count in treated pigs was 2904+/-5397 (mean+/-S.D.) while in the controls it was 6235+/-6705. Mean cyst viability was 5+/-11% (mean+/-S.D.) and 97+/-4% in treated and control pigs, respectively. Results showed that OFZ killed muscular cysticerci over a period of 4 weeks but failed to kill cerebral cysticerci. Antibodies, CCA responses and clearance of dead cysts from the meat, depended on the cyst intensity of individual pigs at time of treatment since both antibody and CCA correlated with intensity of cysticerci at necropsy (r=0.441, P=0.005; r=0.654, P<0.001), respectively. IgG1 responses were the best indicator of treatment efficacy because they were predominant in both infected treated and control pigs and disappeared early after treatment. Both Ab/Ag-ELISA failed to detect cysts in the brain. Though dead cysticerci took some time (26 wkpt) to clear from the meat, treatment of porcine cysticercosis with OFZ should, in combination with other intervention measures be considered as an important, cost-effective measure in the control of taeniosis/cysticercosis.

Two decades of biomonitoring polar bear health in Greenland: a review

SummaryWe present an overview of studies of anthropogenic pollutants in East Greenland polar bears over the period of 1999-2011. East Greenland polar bears are among the most polluted species, not just in the Arctic but globally, and represent an excellent biomonitoring species for levels and effects of global pollution in an apex predator. Therefore, an international multidisciplinary team joined to monitor and assess the patterns and concentrations of contaminants and their potential negative impact on polar bears. The review showed that East Greenland polar bears are exposed to a mix of chlorinated, brominated and fluorinated organic compounds as well as mercury which are all known to have endocrine, immune and organ-system toxic properties. For example, the concentrations of PCBs (polychlorinated biphenyls) in blubber ranged approximately 800-21,000 ng/g lw while mercury concentrations in liver and kidney ranged 0.1-50 μg/g ww. Regarding health endpoints, bone density seemed to decrease as a function of time and OHC (organohalogen compound) concentrations and further T-score for adult males indicated risk for osteoporosis. .The size of sexual organs decreased with increasing OHC concentrations. In the lower brain stem, mercury-associated decreases in NMDA-receptor levels and DNA-methylation was found The present review indicated that age was one of the major drivers for liver and renal lesions, although contaminants and infectious diseases may also play a role. Lesions in thyroid glands were most likely a result of infectious and genetic factors and probably, together with endocrine disrupting chemical (EDCs), the reason for disturbances/fluctuations in blood plasma thyroid hormone concentrations. Except for bone density reductions and neurological measures, all findings were supported by case-control studies of Greenland sledge dogs exposed long-term orally to similar combinations of contaminant concentrations. The studies of sledge dogs also indicated that the mixture of contaminants and fatty acids in the blubber of prey similar to that of polar bears induces cellular as well as humoral immune toxic changes. These controlled studies using model species for polar bears indicate that the correlative findings between health endpoint and contaminants in polar bears could be a cause-and-effect relationship. Physiologically based pharmacokinetic (PBPK) modelling showed that the risk quotients were ≥1 for ΣPCB, dieldrin and PFOS, which indicate an increased risk of prenatally reproductive pathology. In conclusion polar bears are susceptible to long-range transported chemicals that may have various adverse effects on multiple organ systems such as the reproductive and immune system.

Renal lesions in Greenland sledge dogs ( Canis familiaris ) exposed to a natural dietary cocktail of persistent organic pollutants

Persistent organic pollutants such as Polychlorinated biphenyls (PCB) and dichloro diphenyl trichloroethane (DDT) are known to exert various adverse health effects in wildlife mammals. The impact from dietary intake of minke whale (Balaenoptera acutorostrata) blubber high in organohalogen and other chemical contaminants on renal morphology and function was investigated via a controlled study on West Greenland sledge dogs (Canis familiaris). Our results showed significantly higher frequencies of glomerular, tubular, and interstitial lesions in the exposed group. Furthermore, higher urine protein : creatinine ratio and plasma urea levels were found in the exposed group, which indicated a negative impact on kidney function via tubular and glomerular dysfunctions. The lesions were similar to those observed in top predator marine species–such as seals and polar bears–and humans exposed via diet to persistent environmental pollutants. The lesions may have impacts on the overall health of these animals. It is reasonable to suggest that chronic exposure to organic pollutants via a country diet of high trophic level marine organisms may have an impact on renal morphology and function in Arctic apex predators in general as well as Inuit people.

The immune response in Taenia solium neurocysticercosis in pigs is associated with astrogliosis, axonal degeneration and altered blood–brain barrier permeability

Immunohistochemistry was used to examine the immuno-pathological changes and the extent of neuronal damage caused by either viable or dead Taenia solium cysticerci during porcine neurocysticercosis. Thirty pig brains with cerebral cysticercosis and 5 brains from T. solium free pigs were used in this study. Results revealed extensive astrogliosis, neuronal and mostly axonal damage in both early (grade I) and late (grades III and V) lesions as evidenced by an increased expression of glial fibrillary acidic protein (GFAP) and neurofilament protein (NFP). In many late lesions, astrocyte end-feet formed glial scars that surrounded the dead parasite. Rapid angiogenesis resulted in blood vessels lacking astrocyte end-feet suggesting loss of blood-brain barrier (BBB) hence allowing an influx of peripheral blood immune cells such as eosinophils, macrophages, CD3+ T cells, B lymphocytes and plasma cells into lesions. This study showed that porcine NCC was associated with severe nervous tissue damage, the host response of which is a collaborative effort between the local and peripheral immune responses comparable to that observed in human NCC. Results further implied that porcine NCC could be a useful model for understanding the course of NCC in human as well as provide useful information for therapeutic and/or immune strategies.

Chronic dietary exposure to environmental organochlorine contaminants induces thyroid gland lesions in Arctic foxes (Vulpes lagopus).

The impact of dietary organochlorine (OC) exposure on thyroid gland pathology was studied in farmed male Arctic foxes (Vulpes lagopus). The exposed group (n=16) was fed a diet based on wild minke whale (Balaenoptera acutorostrata) blubber as a main fat source in order to mimic the exposure to OC cocktails in the Artic environment. This resulted in an exposure of approximately 17 microg Sigma OC/kg day and a Sigma OC residue adipose tissue and liver concentration of 1700 and 4470 ng/gl.w., respectively, after 16 months of exposure. Control foxes (n=13) were fed a diet with pork (Sus scrofa) fat as a main fat source containing significantly lower OC concentrations. The food composition fed to the control and exposed group was standardized for nutrient contents. Four OC-related histopathological changes were found: (1) flat-epithelial-cell true thyroid cysts (TC) characterized by neutral content; (2) remnants of simple squamous epithelial-cell embryonic ducts containing neutral debris (EDN); (3) remnants of stratified squamous epithelial-cell embryonic ducts containing acid mucins often accompanied with debris of leukocyte inflammatory nature (EDM) and (4) disseminated thyroid C-cell hyperplasia (HPC). Of these, the prevalence of TC, EDN and HPC was significantly highest in the exposed group (chi(2) test: all p<0.04). The study shows that the OC mixture in minke whale blubber may cause development of thyroid gland cysts, C-cell hyperplasia and increase the prevalence of cystic remnants of embryonic ducts. The mechanism causing these effects could include endocrine disruption of the hypothalamus-pituitary-thyroid (HPT) axis, a disturbance of the calcium homeostasis/metabolism or energy metabolism or immune suppression. Because concentrations of OCs are higher in wild Arctic foxes, it is likely that these animals could suffer from similar OC-induced thyroid gland pathological and functional changes.