Liver Tissue Concentrations Research Articles

Oral Exposure to ZnO Nanoparticles Disrupt the Structure of Bone in Young Rats via the OPG/RANK/RANKL/IGF-1 Pathway.

PurposeTo evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action.Materials and MethodsThree-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally.ResultsThe high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P<0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P>0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P<0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P>0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P<0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P<0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P<0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P<0.05), whereas RANKL expression did not change significantly (P>0.05).ConclusionWe infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway.

Effects of Biejia Yugan Granule on rat with ethanol-induced hepatic fibrosis

Objective: To investigate the prevention and treatment effect of Biejia Yugan Granule (BYG) on ethanol-induced hepatic fibrosis (EHF) rats. Methods: SD rats were randomly divided into blank control group, model group, BYG group, colchicine group and BYG low and BYG high dose groups (n=8). The EHF rat model was established by intragastric edible ethanol with a gradually increased dose. Briefly, the rats of model group, colchicine group and BYG low and high dose groups were given gavage of 5 g/(kg·d) ethanol at week 1～4, 7 g/(kg·d) ethanol at week 5～8, 9 g/(kg·d) ethanol at week 9～12 and 9.5 g/(kg·d) ethanol at week 13～24. And the other two groups were treated with equal volume water. At the same time, the corresponding drugs were administrated daily: BYG group was treated with Biejia Yugan Granules 5.55 g/kg, colchicine group was treated with colchicine 0.1 mg/kg, BYG low-dose and high-group were treated with Biejia Yugan Granules 1.85 and 5.55 g/kg respectively. The blank control group and model control group were given the same amount of purified water. On the 169th day of the experiment, the effects of BYG on the macroscopic changes of rat liver organs, the water content of liver tissue and the pathological changes of fibrosis, the content of hydroxy proline (Hyp) in liver tissue and the expression levels of α-SMA and CREB were observed. Results: BYG at the doses of 1.85 and 5.55 g/kg could significantly improve the macroscopic changes of liver and pathological changes of liver tissue fibrosis in rats with EHF, reduce the contents of water and Hyp in liver tissue, and down-regulate the expressions of α-SMA and CREB. Conclusion: BYG has obvious effect on inhibiting EHF and one of its mechanisms is down-regulate the content of CREB.

Hepatic stem cell Numb gene is a potential target of Huang Qi Decoction against cholestatic liver fibrosis

Numb is a negative regulator of Notch signal pathway. Previous study has demonstrated that Notch signal pathway activation is required for hepatic progenitor cell (HPC) differentiating into cholangiocytes in cholestatic liver fibrosis (CLF), and Huang Qi Decoction (HQD) could prevent CLF through inhibition of the Notch signal pathway. However, the role of Numb in HQD against CLF is yet unclear. Thus, CLF rats transplanted into rat bone marrow-derived mesenchymal stem cells with knocked down Numb gene (BMSCNumb-KD) were treated with HQD. Simultaneously, Numb gene knockdown was also performed in WB-F344 cell line and then treated with refined HQD in vitro. In vivo study revealed that liver fibrosis was inhibited by HQD plus BMSCNumb-KD treatment, while Hyp content in liver tissue, the gene and protein expression of α-SMA, gene expression of Col I, TNF-α, and TGF-β1 were increased compared to that in HQD group. Furthermore, Notch signal pathway was inhibited by HQD plus BMSCNumb-KD, while the protein expression of Numb was decreased and RBP-Jκ and Hes1 was increased compared to that in HQD group. In vitro, HQD reduced the differentiation of WB-F344 cells into cholangiocyte phenotype, while this effect was attenuated after Numb-knockdown. This study highlights that the absence of hepatic stem cell Numb gene decreases effect of HQD against CLF, which give rise the conclusion that Numb might be a potential target for HQD against CLF.

Biochemical studies on the antidiabetic properties of immature palmyra palm fruits studied in high fat diet fed-low dose streptozotocin induced type 2 diabetes in rats

Borassus flabellifer Linn. commonly known as the “Palm tree” is a tall, erect and celestial tree with more than 800 established uses. The immature palmyra palm fruits have been traditionally used for the treatment of diabetes and its secondary complications. In the absence of systemic reports in the literature, the present study was aimed to evaluate the antidiabetic and antioxidant properties of the immature fruits in High fat diet-fed low-dose STZ induced experimental type 2 diabetes in rats. Diabetic rats were orally treated with palmyra palm fruits extract at a concentration of 400 mg/kg b.w. for 30 days. Oral glucose tolerance test was performed. The levels of fasting blood glucose, plasma insulin, HbA1c, HOMA-IR values were estimated. The activities of key enzymes involved in carbohydrate and glycogen metabolism in the liver and kidney tissues were assayed. The glycogen content in liver tissue was estimated. Chemical analysis evidenced the presence of pharmacologically important phytochemicals and the significant levels of phenolic and flavonoid content in the fruit extract. The alterations observed in the diabetic rats on the important biochemical indices such as fasting blood glucose, insulin, hemoglobulin, and glycosylated hemoglobulin were reverted to the physiological range after oral treatment with fruits extract. Likewise, the altered levels of protein, urea, uric acid and creatinine were normalized after treatment with fruits extract. The assay of activities of regulatory enzymes revealed the role of fruits extract in the regulation of carbohydrate and glycogen metabolism. The results of the present study provide substantial evidence for the rationale and antidiabetic properties of immature palmyra palm fruits extract.

Beneficial effect of black rice ( Oryza sativa L. var. japonica ) extract on amyloid β-induced cognitive dysfunction in a mouse model.

Alzheimer's disease (AD) is an age-dependent progressive neurodegenerative disease, resulting in memory loss and cognitive dysfunction. The accumulation of amyloid β (Aβ) has been identified as the most important risk factor for AD. Black rice (BR; Oryza sativa L. var. japonica), which is widely consumed in Asia, is a good source of bioactive compounds including anthocyanins. Therefore, the aim of the present study was to evaluate the protective effect of BR extracts against Aβ25-35-induced memory impairment in an in vivo AD mouse model. After intracerebroventricular injection of Aβ25-35, mice were treated with BR extract supplementation for 14 days. Memory and cognition function were evaluated over this period in both treated and untreated animals using T-maze, novel object recognition and Morris water maze tests. After behavioral tests, malondialdehyde (MDA) and nitric oxide (NO) concentrations in brain, liver and kidney tissues were analyzed. Mice treated with Aβ25-35 had impaired memory and cognitive function; however, mice administered BR extract (100 mg/kg/day) demonstrated an improvement in cognition and memory function compared with the Aβ25-35-injected control group. Furthermore, injection of Aβ25-35 significantly increased MDA and NO generation in the brain, liver and kidney of mice. However, the group administered with BR extract had significantly inhibited lipid peroxidation and NO generation in the brain, liver and kidney. In addition, the protective effect of BR on lipid peroxidation and NO production by Aβ25-35 was stronger in the brain compared with other tissues. Collectively, these findings suggested that BR supplementation may prevent memory and cognition deficits caused by Aβ25-35-induced oxidative stress.

Postmortem Liver and Kidney Tissue Concentrations of Heroin Biomarkers and Their Metabolites in Heroin‐Related Fatalities*†

A method was developed and validated for analyzing 6-monoacetylmorphine, morphine, 6-acetylcodeine, and codeine in routine postmortem liver and kidney specimens using liquid chromatography-tandem mass spectrometry. Samples were prepared with a Stomacher instrument followed by solid-phase extraction. All calibration curves [0.5-1000ng/g] were linear with coefficients of determination greater than 0.99 and limits of quantification of 1.0ng/g. Within-run precision ranged between 2.0% and 8.0%, between-run precision ranged between 1.0% and 9.0%, and accuracy ranged between -5.0% and +3.0%. Matrix effects ranged from -18% to +9%. After matrix effects were excluded, analytical recoveries ranged from 76% to 94%. The distributions of 6-monoacetylmorphine, morphine, 6-acetylcodeine, and codeine were investigated in 31 postmortem cases in which heroin was the primary cause of death. In the current study, the median free morphine ratios were calculated for liver to blood and kidney to blood, which were 2.2 and 4.0, respectively. The current report highlights the importance of testing multiple specimens, including liver and kidney, in heroin-related deaths, especially if no blood samples are available. Furthermore, this work presents new information regarding the distribution of heroin metabolites in liver and kidney.

A seasonal comparison of trace metal concentrations in the tissues of Arctic charr (Salvelinus alpinus) in Northern Québec, Canada.

Ecotoxicological research detailing trace metal contamination and seasonal variation in the tissues of northern fishes such as Arctic charr (Salvelinus alpinus) has been poorly represented in the literature beyond examination of mercury. In an effort to address this, anadromous Arctic charr were collected from the Deception River watershed in the late summer and post-winter season, before quantifying seasonal and organotropic variations in dorsal muscle and liver concentrations of arsenic, cadmium, chromium, copper, nickel, lead, and zinc. Potential linkages with biological variables (fork length, age, and somatic condition) and indicators of feeding behavior (δ13C and δ15N) were also assessed. Trace metal organotropism favouring elevation in liver tissue concentrations was exhibited by cadmium, copper, nickel and zinc, while arsenic, chromium and lead exhibited no significant organotropic variation. Seasonal differences in concentrations were metal and tissue dependent, but generally increased in tissues collected from post-winter sampled Arctic charr. Significant correlations with biological and trophic descriptors were also determined to be element and tissue dependent. These parameters, in addition to season, were incorporated into multi-predictor variable models, where variations in trace metal concentration data were often best explained when season, somatic condition, and trophic descriptors were included. These variables were also of greatest relative importance across all considered trace metals and tissue types. These findings suggest that seasonally linked processes have the greatest influence on trace metal concentrations in anadromous Arctic charr. Future metal-related research on Arctic charr and other northern fish species should further consider these variables when evaluating elemental accumulation.

Baiting location affects anticoagulant rodenticide exposure of non-target small mammals on farms.

Commensal rodents such as Norway rats (Rattus norvegicus Berk.), black rats (R. rattus L.) and house mice (Mus musculus L.) damage stored produce and infrastructure, cause hygienic problems and transmit zoonotic pathogens to humans. The management of commensal rodents relies mainly on the use of anticoagulant rodenticides (ARs). ARs are persistent and bio-accumulative, which can cause exposure of non-target species. We compared the baiting strategies to use brodifacoum (BR) in bait boxes indoors only versus in and around buildings in replicated field trials at livestock farms to assess resulting BR residues in non-target small mammals. When bait was used indoors only, the percentage of trapped non-target small mammals with BR residues as well as BR concentration in liver tissue was about 50% lower in comparison to bait application in and around buildings. These effects occurred in murid rodents and shrews but not in voles that were generally only mildly exposed. During the baiting period, BR concentration in murids was stable but decreased by about 50% in shrews. Restricting the application of BR bait to indoors only can reduce exposure of non-target species. The positive effect of this baiting strategy on non-target species needs to be balanced with the need for an effective pest rodent management within a reasonable time. More research is needed to clarify which management approaches strike this balance best.

Comparison of the metal concentrations in muscle and liver tissues of fishes from the Erren River, Southwestern Taiwan, after the restoration in 2000

Metal concentrations in the muscle and liver tissues of fishes from the Erren River in southwestern Taiwan were analyzed to evaluate the pollution status after the completion of the restoration plan in 2000. It was the first time the tissue concentrations of 4 important elements, i.e. Fe, Mn, As and Hg, were reported in fishes from this area. Samples were collected in January 2002 at the junction of the Erren River and the Sanyegong River, the most polluted section of the river. Five fish species, Megalops cyprinoids (Indo-Pacific tarpon), Chanos chanos (milkfish), Liza macrolepis (large-scaled mullet), Mugil cephalus (striped mullet) and Orechromis sp. (tilapia) were collected. A total of 91 fishes were dissected and the muscle and liver tissues taken for analysis of seven metals, Fe, Zn, Cu, Mn, As, Hg and Cd, on a wet weight basis (mg/kg). Among them, Fe and Zn were the highest, followed by Cu, Mn and As, while the Hg and Cd concentrations were the lowest. Except for As and Hg, which showed higher concentrations in the muscle tissues than in the livers, the remaining elements showed higher concentrations in livers. Significant species differences were found in all elements and tissues. The highest concentrations of Fe, Zn, Cu and Mn in muscles were found in tilapia (4.04), striped mullet (4.38), large-scaled mullet (0.20) and milkfish (0.534), respectively. The highest concentrations of As and Hg were found in striped mullet (1.59) and Indo-Pacific tarpon (0.081), respectively. The highest concentrations of Fe (3122), Hg (0.045) and Cd (0.123) were found in livers of large-scaled mullet, while striped mullet had the highest concentration of Zn (77.6), Cu (78.2) and As (2.39). The level of Mn in tilapia was 1.32 mg/kg. The Zn, Cu and Cd concentrations of the muscles and livers were mostly 7-50% lower than the levels reported on the same species of the same tissue before the restoration indicating the improvement on the metal pollution status. The heavy metal concentrations in this area were similar to various uncontaminated areas around Taiwan and all were within the food standard levels of the FDA and NHMRC.

Eicosapentaenoic and docosahexaenoic acid supplementation during early gestation modified relative abundance on placenta and fetal liver tissue mRNA and concentration pattern of fatty acids in fetal liver and fetal central nervous system of sheep.

In sheep, polyunsaturated fatty acid (PUFA) supplementations in late gestation increases the growth of offspring; however, there is a lack of evidence on the effect of PUFA supplementation during early gestation. Thus, the objective of this study was to evaluate the effect of dietary supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in early gestation pregnant ewes on fatty acid concentration of fetal liver (FL) and fetal central nervous system (FCNS), and relative abundance of the mRNA for genes associated with transport and metabolism of fatty acids in FL and placenta. A total of 12 ewes, block for stage of gestation were fed a diet containing 1.6% (dry matter basis) monounsaturated fatty acids (MUFA) or EPA+DHA during the first 45 days of gestation. A cesarean section was conducted on day 45 of gestation to collect placenta (caruncle and cotyledon), FL, and FCNS. Relative abundance of mRNA in FL and FCNS and fatty acid concentration were analyzed using a 2x2 factorial arrangement of treatments considering fatty acid supplementation and tissue as the main factors. Concentrations of C18:1 isomers increase (P < 0.05) in FL and FCNS with MUFA supplementation; the FL and FCNS had a greater concentration of C20:3(n-6), C20:3(n-3), C22:1, C22:5 and C22:6 (P < 0.05) with EPA+DHA supplementation. In FL, the relative abundance of LPL mRNA was greater (P = 0.02) as a result of MUFA supplementation. In placenta, there was a FA x tissue interaction for relative abundance of DNMT3b and FFAR-4 mRNA (P < 0.05). Fetus from MUFA-supplemented dams had a greater relative abundance of FABP-4 mRNA (P < 0.05). Results indicate supplementation with EPA+DHA during early gestation increases the total EPA and DHA in FL. For the placenta, EPA+DHA supplementation led to an increase in the relative abundance of lipid mRNA for transport genes.

Hypermethylation of MT1G and MT1H CpGs Promoter Sites and High Serum Levels of Cu Affect Survival Rate of Patients Affected by Hepatocellular Carcinoma

Abstract Objectives Recent evidences suggest a principal role of trace elements and metallothioneins (MTs), proteins involved in metal ions homeostasis and detoxification, in hepatocellular carcinogenesis. The study was designed to evaluate whether serum and liver tissue concentrations of the trace elements Cu, Zn and Se are implicated in survival rate of hepatocellular carcinoma (HCC) patients and if promoter DNA methylation is involved in trace elements-related proteins regulation. Methods Cu, Zn and Se levels were determined in serum and liver tissue samples, both HCC and homologous non neoplastic tissue (N) of 27 HCC patients by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Gene expression analysis of MT1G and MT1H, was performed by Real-time qPCR in HCC and N tissue. Promoter DNA methylation of a region overlapping MT1G and MT1H promoters was assessed by bisulfite amplicon sequencing (BSAS) in HCC and N tissues of 23 patients. Kaplan-Meier survival curves were drawn using the log-rank test (Mantel-Cox test) to examine the differences in survival according to serum trace elements and to gene-specific methylation levels. Results Kaplan-Meier analysis according to serum Cu levels showed that subjects within the highest quintile had an increased mortality rate (88.9%) compared with the other four quintiles (P = 0.025). Considering the 80th percentile of Cu levels (1118 μg/L), subjects with Cu concentrations above this value had a significantly decreased survival rate (P &amp;lt; 0.001). Se and Zn content were depleted in HCC tissues as compared to N tissues (P &amp;lt; 0.0001). MT1G and MT1H were strongly repressed in HCC tissues and precisely, MT1H in 24 out of 27 HCC tissues (P = 0.008) and MT1G in 23 out of 27 HCC tissues (P = 0.037). Nine out of 19 HCC tissues showing a down-regulation of MTs with three CpG sites, significantly hypermethylated in HCC tissue as compared to N tissue (P &amp;lt; 0.05). Considering the median methylation level, patients with higher methylation values showed increased mortality rate (P = 0.015). Conclusions The significant repression of MT1G and MT1H in HCC tissue is related to promoter hypermethylation and support the hypothesis of MT1G and MT1H as possible tumor suppressor genes in HCC. The evidence of promoter methylation levels and survival rate association provide new insights for the role of DNA methylation in liver carcinogenesis. Funding Sources N/A.

Intrahepatic Arterial Delivery of Sorafenib Eluting Beads: A Pharmacokinetics Study

Objective: To determine the slow-release effect of Sorafenib carried beads and its impact on the normal liver of dogs. Materials and Methods: (1) To obtain the maximal drug-carrying of beads, different sizes of beads (300-500 μm and 500-700 μm) were tried. Five bottles of different sizes of beads were added into 75% solution of Sorafenid-alcohol with different concentrations: Bottle a,50mg/20ml; Bottle b, 100mg/20ml; Bottle c, 100 mg/40ml; Bottle d, 200mg/40m; Bottle e, 250mg/50ml. (2) In vivo study: 12 dogs were randomly divided into four groups [group A, Sorafenib carried bead (500-700μm); group B, only bead (300-500μm) ; group C, Lipiodol-sorafenib and four dogs in each group. Each group was treated with TAE with emulsion mentioned above. Sorafenib concentration in plasma and liver tissue was determined with HPLC respectively. Result: (1) In vitro research: Sorafenib can be dissolved into 75% alcohol and the best concentration for drug-carrying was 100mg/20ml. (2) In vivo study: ① Compared with group D, the Cmax and AUC in plasma in group A and B has a significant statistics difference(p&lt;0.05). ② Sorafenib concentration in liver tissue could be determined in group A in the 3rd day and even after one week while it could not be determined in group D. Conclusion: Sorafenib can be carried in DC-Bead in a certain condition. Compared with emulsion with Sorafenib and lipiodol, DC-bead has a definite slow-release function and it is superior to lipiodol.

Patterns of Trace Element Accumulation in Waterfowl Restricted to Impoundments Holding Coal Combustion Waste.

Waterfowl are often exposed to and readily accumulate anthropogenic contaminants when foraging in polluted environments. Settling impoundments containing coal combustion waste (CCW) enriched in trace elements such as arsenic (As), selenium (Se), and mercury (Hg) are often used by free-ranging migratory and resident waterfowl and represent potential sources for contaminant uptake. To assess accumulation of CCW contaminants, we experimentally restricted waterfowl to a CCW-contaminated impoundment and quantified trace element burdens in blood, muscle, and liver tissues over known periods of exposure (between 3 and 92 d). From these data we developed models 1) to predict elemental bioaccumulation with increased exposure time, and 2) to predict muscle/liver burdens based on concentrations in blood as a nondestructive sampling method. Although Hg and As did not bioaccumulate in our waterfowl, we observed an increase in Se concentrations in muscle, liver, and blood tissues over the duration of our experiment. Furthermore, we found that blood may be used as an effective nondestructive sampling alternative to predict muscle and liver tissue concentrations in birds contaminated with Se and As through dietary exposure. These data provide unique insights into accumulation rates of contaminants for waterfowl utilizing habitats contaminated with CCW and demonstrate the efficacy of nonlethal sampling of waterfowl to quantify contaminant exposure. Environ Toxicol Chem 2020;39:1052-1059. © 2020 SETAC.

Chlorinated Paraffins in Two Snake Species from the Yangtze River Delta: Tissue Distribution and Biomagnification

Very-short, short-, medium-, and long-chain chlorinated paraffins (vSCCPs, SCCPs, MCCPs, and LCCPs, respectively) were analyzed in different tissues of the terrestrial short-tailed mamushi (Gloydius brevicaudus) and the semi-aquatic red-backed rat snake (Elaphe rufodorsata) from the Yangtze River Delta, China. The total CP concentrations in liver, muscle, and adipose tissues in the two snake species were in the range of 2500-24 000, 4900-48 000, and 12-630 ng/g lw, respectively. Tissue burdens indicated that vSCCPs (C6-9) and SCCPs (C10-13) preferentially distributed to snake liver, while adipose was an important storage site and sink of MCCPs (C14-17) and LCCPs (C>18). On a lipid weight basis, vSCCPs and SCCPs were found in highest concentrations in red-backed rat snake liver and MCCPs and LCCPs in muscle, whereas for short-tailed mamushi, all CP groups were predominant in muscle, probably reflecting ecosystem/food web differences. Moreover, vSCCPs, SCCPs, MCCPs, and LCCPs were found to be biomagnified from black-spotted frogs to red-backed rat snakes with mean (maximum) biomagnification factors of 2.2 (3.4), 1.9 (3.7), 1.8 (2.8), and 1.7 (4.5), respectively. This is the first field study of biomagnification potential involving vSCCPs and LCCPs and highlights the need to include all CPs in studies.

Influence of demographics, exposure, and habitat use in an urban, coastal river on tumor prevalence in a demersal fish

Neoplasia and associated tissue biomarkers in benthic fishes are commonly used to characterize effects of contaminated sediments in aquatic ecosystems. However, these fish are often migratory or partially-migratory, and thus assessing the effect of location-specific contamination is challenging because the fish will have a complex exposure history. We determined liver and skin neoplasia prevalence for a benthic, partially-migratory fish, white sucker (Catostomus commersonii), and used carbon and nitrogen stable isotope ratios to determine the diet contribution associated with areas of contaminated sediments within the urbanized portion of the St. Louis River. We then tested which factors were significantly related to neoplasia prevalence, including age, sex, and the percent diet obtained from contaminated areas within the St. Louis River relative to Lake Superior, the reference area. Overall, the prevalence of contaminant-related internal and external tumors was low, <5%. For skin neoplasia prevalence, both sex and age were significant factors, whereas location-specific diet contribution based on stable isotope analysis was not a significant factor. For liver neoplasia prevalence, only age was a significant factor. Nevertheless, for all contaminants measured (polychlorinated biphenyls [PCBs], polychlorinated dibenzodioxins [PCDDs], and polychlorinated dibenzofurans [PCDFs]), there was a significant, negative correlation between liver tissue concentration and Lake Superior diet contribution, confirming that the St. Louis River is the primary source of contaminant exposure. The research highlights the complexity of exposure to location-specific contaminants and potentially infectious agents associated with neoplasia at urban, contaminated sites in the Great Lakes, and elsewhere. It also demonstrates the need to determine the full set of risk factors across life-stages, habitats, and biological endpoints.

Evaluation of two contrasted activated carbon-based sequestration strategies to reduce soil-bound chlordecone bioavailability in piglets.

Chlordecone (Kepone) (CLD) is a highly persistent pesticide formerly used in the French West Indies. High levels of this pesticide are still found in soils and represent a subsequent source of contamination for outdoor-reared animals which may ingest involuntary non negligible amounts of soil. In that context, sequestering matrices like activated carbons (ACs) may be used to efficiently decrease the bioavailability of such organic pollutants. The present study intends to assess the respective efficiency of two sequestering strategies where two different ACs were provided either via feed incorporation or via soil amendment. This study involved 20 piglets randomly distributed into 5 experimental groups (4 replicates). All groups were exposed to 10 μg of CLD per kg of BW per day during 10 days via a contaminated soil. In both "Soil-ACs" treatment groups, the contaminated soil was amended by 2% (mass basis) of one of the two ACs. The two "Feed-ACs" groups received the contaminated soil and one dough ball containing 0.5% (mass basis) of one of the ACs. The piglets were then euthanized before collection of pericaudal adipose tissue and the whole liver and CLD analysis. A significant decrease of CLD concentrations in liver and adipose tissue was observed only in the "Soil-ACs" groups in comparison with the control group (P < 0.001). This decrease was particularly important for the coconut shell activated carbon where relative bioavailability was found lower than 1.8% for both tissues.

P.586 Comorbid depression in patients with schizophrenia: does it have an impact on their neurocognitive functioning?

Historically, the European Atlantic is probably the most important oil-spill hotspot worldwide. One of the most recent accidents occurred in 2002 when the oil-tanker Prestige sank over the Galician Bank causing two major oil-spills followed by several small leaks until March 2003. This resulted in contamination of virtually all types of marine habitat. Considering that parasites have proved to be good effect and accumulation bioindicators, the present study addresses the medium-term changes in trace element content after the Prestige oil-spill in a model host-parasite system, the bogue, Boops boops (Sparidae) and the isopod Ceratothoa oestroides. To our knowledge, this study is the first to address trace element concentrations in natural fish and parasite populations associated with the effects of an oil-spill. We observed that both test organisms examined, the host and the parasite, indicate a detectable change in the relative composition of trace element concentrations before and after the Prestige oil-spill. Multivariate analyses also indicated a differential response of the different tissues to the temporal sampling sequence. However, analyses of both host and parasite tissues supported the pattern of a gradual temporal transition to a state of relative trace element content distinctly departing from the pre-spill situation. Moreover, the parasite-host element accumulation ratios better depicted this temporal pattern. Additionally, changes in V concentrations in fish liver tissues and Ni concentrations in the parasite tissues suggest that this host-parasite system may be a useful tool to assess these two element contaminations linked to heavy fuel oil-spill.

Effects of stress-induced increases of corticosterone on circulating triglyceride levels, biliverdin concentration, and heme oxygenase expression

When exposed to stressors, animals physiologically respond by secreting glucocorticoid hormones. Most birds, reptiles, and amphibians secrete corticosterone (CORT), which allows them to maximize short-term survival, including by modulating lipid metabolism. However, the factors regulating lipid metabolism, particularly during acute (i.e., short-term) stressors, are not well-characterized. To investigate one putative mechanism, we examined how expression of the enzyme heme oxygenase (HO), which primarily converts heme into biliverdin, changes during an acute stressor. Because HO has links to decreased levels of triglycerides, we tested the hypothesis that an acute stressor increases HO expression, which would concomitantly decrease circulating lipid levels. We compared free-living house sparrow (Passer domesticus) nestlings exposed to a one-hour stressor to control individuals, and quantified HO expression and biliverdin concentration in spleen, liver, or kidney tissue, as well as circulating CORT, triglyceride, and glycerol levels. Nestlings exposed to a stressor had reduced circulating triglycerides consistent with an increased rate of gluconeogenesis during an acute stressor. Concentrations of triglycerides were also negatively correlated with HO expression in the liver, which is consistent with mammalian studies. However, contrary to our predictions, exposure to a stressor did not affect HO expression, or biliverdin concentration in liver, spleen, or kidney. Overall, our results support links between CORT, triglyceride levels, and HO expression, though the molecular pathways connecting these metrics still need to be elucidated.

Wilson disease.

Wilson disease (WD) is an inherited disorder of copper metabolism. The resultant defective handling of copper results in toxic effects on the hepatocytes and increased copper in the circulation. Copper accumulates in other organ sites especially the central nervous system. WD occurs worldwide, usually between 5 and 35 years; a wider age range is now recognized. Clinical presentations are diverse and include combinations of hepatic, neurological, ophthalmic and psychiatric manifestations. Biochemical abnormalities such as serum ceruloplasmin and 24-h urinary copper excretion are important for the diagnosis but are not always abnormal in WD. They can overlap with non-WD causes. Patients may present with hepatic or neurological disease or combinations thereof. Approx. 50% of WD patients present with liver disease. Liver presentation is variable: asymptomatic abnormal liver tests, chronic hepatitis picture, cirrhosis, and acute liver failure. Similarly, the histology has several different patterns: mild nonspecific changes, steatosis or steatohepatitis, chronic hepatitis, and acute hepatitis with submassive or massive necrosis. None of these are specific for WD. Aids to the histologic diagnosis include special stains for copper and copper associated protein, and copper concentration in liver tissue. The biopsy is performed in the context of the clinical algorithms for the diagnosis of WD put forth by the clinical hepatology organizations such as the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease. The discovery of the responsible gene ATP7B has made the molecular diagnosis feasible through genetic testing and sequencing of the gene.

Protective Effects of Fucoxanthin against Alcoholic Liver Injury by Activation of Nrf2-Mediated Antioxidant Defense and Inhibition of TLR4-Mediated Inflammation.

Fucoxanthin (Fx) is a natural extract from marine seaweed that has strong antioxidant activity and a variety of other bioactive effects. This study elucidated the protective mechanism of Fx on alcoholic liver injury. Administration of Fx was associated with lower pathological effects in liver tissue and lower serum marker concentrations for liver damage induced by alcohol. Fx also alleviated oxidative stress, and lowered the level of oxides and inflammation in liver tissue. Results indicate that Fx attenuated alcohol-induced oxidative lesions and inflammatory responses by activating the nuclear factor erythrocyte-2-related factor 2 (Nrf2)-mediated signaling pathway and down-regulating the expression of the toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway, respectively. Our findings suggest that Fx can be developed as a potential nutraceutical for preventing alcohol-induced liver injury in the future.