Metal Levels In Liver Research Articles

The ethylene bisdithiocarbamate fungicides mancozeb and nabam alter essential metal levels in liver and kidney and glutathione enzyme activity in liver of Sprague-Dawley rats

Mancozeb is a fungicide of the ethylene bisdithiocarbamate (EBDC) class complexed to the metals manganese and zinc. Nabam is the sodium salt of the EBDC backbone. The purpose of this study was to determine if these EBDC compounds alter essential metal homeostasis and glutathione status in Sprague-Dawley rats. Our findings indicate EBDCs caused accumulation of copper in kidneys, but not liver. EBDC compounds also increased glutathione reductase activity in liver, but not kidneys, whereas only mancozeb increased glutathione peroxidase activity in the liver. Mancozeb and nabam increased total glutathione in liver, but only mancozeb increased total glutathione in the kidney. Neither mancozeb nor nabam altered glutathione ratio in either liver or kidney compared to control. Our data suggest that the EBDC backbone of mancozeb, and not the zinc or manganese moieties, is responsible for changes in glutathione status and alteration of essential metal homeostasis in rat liver and kidney.

Hepatic and renal histology and mercury concentrations of North West and North East Greenland narwhals (Monodon monoceros)

ABSTRACTNarwhals (Monodon monoceros) are at the top of the Arctic food web and therefore might biomagnify high total mercury (Hg) concentrations in organs and tissues. The aim of this study was to determine histopathology and Hg concentrations in liver and kidneys from 15 North East Greenland narwhals (3 subadult females, 8 adult females, 3 subadult males, and 1 adult male) and compare data with previous observations of 12 North West Greenland specimens (1 subadult female, 4 adult females, 1 subadult male, and 6 adult males). The zoological length was significantly larger and hepatic and renal concentrations significantly higher in adults compared to subadults. When comparing tissues, the Hg levels were significantly the highest in liver, while a correlation between metal levels in liver and kidneys was positive and significant. Histological examination of renal tissues presented four types of glomerular lesions (capillary dilatation [0–100%], membrane thickening [0–100%], dilatation of space [0–80%], and sclerosis [0–70%]) and two tubular lesions (atrophy/hyalinization [0–40%] and casts [0–60%]). Hepatic tissues exhibited three portal lesions (fibrosis [0–33%], cell infiltrates [0–40%], and bile duct proliferation [0–40%]) and two parenchymal lesions (steatosis [83–100%] and lipid-filled Ito cells [0–33%]). All 12 lesions were found in adult whales from North West Greenland while eight were present in adult whales from North East Greenland. Six lesions were detected in subadults from North East Greenland and four in subadults from North West Greenland. A significantly higher frequency of dilatation and hyalinization of Bowman’s space and capsule and glomerular capillary dilatation was found in adult narwhals from West Greenland. There was no marked difference in Hg concentrations in whales with and without histological lesions. In conclusion, the prevalence of histological changes and Hg levels were the highest in adults and therefore both age and metal are important factors to include when evaluating liver and kidney lesions in narwhals.

Liver metal levels and expression of genes related to iron homeostasis in rhesus monkeys after inhalational manganese exposure.

Here we present data on liver metal levels and expression of genes related to iron homeostasis in rhesus monkeys after inhalational manganese exposure. Archived liver samples from rhesus monkeys exposed to 0 (n=6), 0.06 (n=6), 0.3 (n=4) and 1.5 (n=4) mg/m3 manganese inhalation for 65 days were obtained from a published study (“Tissue manganese concentrations in young male rhesus monkeys following subchronic manganese sulfate inhalation” [1]). Samples were analyzed by spectroscopy, immunoblotting and quantitative PCR to assess metal levels and gene expression. Liver manganese and iron levels were linearly correlated although only the intermediate manganese exposure level (0.3 mg Mn/m3) led to a statistically significant increase in liver iron levels.

Effect of Hfe Deficiency on Memory Capacity and Motor Coordination after Manganese Exposure by Drinking Water in Mice.

Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout (Hfe-/-) and their control wild-type (Hfe+/+) mice to MnCl2 in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in Hfe+/+ mice, but not in Hfe-/- mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed Hfe+/+ compared with water-drinking Hfe+/+ mice. However, Mn-exposed Hfe-/- mice spent more time to find the target hole than Mn-drinking Hfe+/+ mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and other iron overload disorders.

Heavy metal and trace element bioaccumulation in target tissues of four edible fish species from the Danube River (Serbia)

Pikeperch (Sander lucioperca), European catfish (Silurus glanis), burbot (Lota lota), and common carp (Cyprinus carpio) were collected from the Danube River (Belgrade section, Serbia), and samples of liver, muscle, and gills were analyzed for Al, As, B, Ba, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Ni, Pb, Se, Sr, and Zn using inductively coupled plasma optical emission spectrometry (ICP-OES) to highlight the importance of species and tissue selection in monitoring research, contaminant studies, and human health research. The Kruskal–Wallis test revealed significant differences between fish species in regard to metal levels in liver, muscle, and gills. The principal component analysis (PCA) indicated that the studied fish species could be grouped on the basis of the level of analyzed elements in liver and gills. The Mann–Whitney test showed two subsets (one comprising two piscivorous species, pikeperch and catfish, and the other, two polyphagous species, burbot and carp) in regard to Cr and Hg levels in liver (higher levels in piscivorous species), as well as B, Fe, and Hg in gills (B and Fe with higher levels in polyphagous and Hg in piscivorous species), and As in muscle (higher levels in polyphagous species). Carp had distinctly higher levels of Cd, Cu, and Zn in liver in comparison to other three species. None of the elements exceeded the maximum acceptable concentrations (MAC). However, since Hg levels are close to the prescribed MAC levels, the consumption of these fishes can be potentially hazardous for humans.

Metallothionein and metal levels in liver, gills and kidney of Sparus aurata exposed to sublethal doses of cadmium and copper

The levels of metallothionein (MT), a biomarker of metal exposure, and of Cd and Cu, known as MT inducers, were investigated in Sparus aurata intraperitoneally injected with 500 microg/kg of Cu and Cd for 2 days. MT and metal concentrations (Cd and Cu) were determined in liver, gills and kidney. MT levels were significantly increased in all investigated tissues, with the highest value in liver of Cu as Cd-treated fishes (3.56-fold and 3.3- fold, respectively). Metal concentrations were statistically different between all tissues. Highest metal concentrations were in the liver. The higher metal concentrations and MT induction levels support the main role of MT in metal homeostasis and detoxification.

Heavy Metal Accumulation in Four Species of Sea Turtles from the Baja California Peninsula, Mexico

Heavy metals were assessed in four species of sea turtles from the Baja California Peninsula, Mexico, representing the first report of heavy metal concentrations in tissues of post-yearling sea turtles from the Eastern Pacific. Concentrations of Cd measured in C. mydas kidney (653 microg/g dry wt) were the highest ever reported for any sea turtle species. Cd accumulated preferentially in kidney and the ratios of kidney to liver Cd in Baja California turtles were among the highest reported for sea turtles globally. Zn, Ni, and Mn concentrations were also significantly higher in kidney than other tissues, while Cu and Fe were greatest in liver, and all metals were lowest in muscle. With the exception of one value (69.9 microg/g in kidney of C. caretta), Pb was low in all tissues from Baja California. In comparisons across species, kidney of C. mydas had greater Zn and Ni concentrations as compared to other species, although there was no difference in liver metal levels among the species. Positive correlations were detected in the concentrations of Cd, Cu and Ni with the straight carapace length of C. caretta.

Toxicity and bioaccumulation of heavy metals in mullet fish Liza klunzingeri (Mugilidae: Perciformes)

The mullet fish, Liza klunzingeri, commercially important and widely relished by Kuwaiti residents, and the stressed ecosystem in Kuwait Bay instigated us to conduct toxicity and bioaccumulation tests on heavy metals (Pb, Ni, V, Cu and Fe). Among five metals, Pb had the lowest observed effect concentration (LOEC) at 1 μg l −1. Using multi-factor Probit analysis, toxicity tests (72 h) on L. klunzingeri reared in filtered sea water in the laboratory showed Pb with maximum effect at median lethal concentration (LC50) followed by V, Ni, Cu and Fe. Their bioaccumulation factor (BAF) was in the sequence Pb>V>Fe>Cu and Ni. For fish exposed for 30 d, bioaccumulation exhibited increasing metal levels in liver followed by gills and muscles. These results suggest the potential use of L. klunzingeri as a bioindicator of metal pollution in the future.

Human exposure to contaminants in the traditional Greenland diet

The traditional diet is a significant source of contaminants to people in Greenland, although contaminant levels vary widely among species and tissue from very low in many to very high in a few. Our study has included cadmium, mercury, selenium, polychlorinated biphenyls (PCB), dichlorophenyltrichloroethane (DDT), chlordane, hexachlorocyclohexanes (HCH), chlorobenzenes, dieldrin and toxaphene in the major species and tissues consumed by Greenlanders. In general, the levels of these are very low in terrestrial species and in muscle of many marine species. High organochlorines concentrations are typically found in blubber of marine mammals and high metal levels in liver and kidney of seals and whales. In this study, the mean intakes of cadmium, chlordanes and toxaphene significantly exceed ‘acceptable/tolerable intakes’ (ADI/TDI) by a factor between 2.5 and 6. Mean intakes of mercury, PCB and dieldrin also exceed ADI/TDI by up to approximately 50%. However as these figures are mean intakes and as variation in both food intake and contaminant levels is large, the variation of contaminant intake among individuals is also large, and some individuals will be exposed to significantly higher intakes. The mean intakes of DDT, HCH and chlorobenzenes are well below the ADI/TDI values, and it seems unlikely that the TDI for these contaminants normally is exceeded in the Greenland population. The evaluation of contaminant intake in this study points to seal muscle, seal liver, seal kidney, seal blubber and whale blubber as the dominant contributors of contaminants in the traditional diet. Levels in liver from Greenland halibut, snow crab, king eider, kittiwake, beluga and narwhal and kidney of beluga and narwhal are also high but were, with the exception of toxaphene in Greenland halibut liver, not important sources in this study, because they were eaten in low quantities. A way to minimize contaminant intake would be to avoid or limit the consumption of diet items with high contaminant levels. If we assume a traditional diet composition in this study without fish liver, bird liver, seal liver, seal kidney, seal blubber, whale liver, whale kidney and whale blubber, the intake of all contaminants would be below the TDIs for these. This will result in a reduction of the intake of the amount of traditional food of only 24–25%, and it is not likely that this changed diet will result in deficiency of minerals, vitamins or other nutritional compounds.

Human exposure to contaminants in the traditional Greenland diet

The traditional diet is a significant source of contaminants to people in Greenland, although contaminant levels vary widely among species and tissue from very low in many to very high in a few. Our study has included cadmium, mercury, selenium, polychlorinated biphenyls (PCB), dichlorophenyltrichloroethane (DDT), chlordane, hexachlorocyclohexanes (HCH), chlorobenzenes, dieldrin and toxaphene in the major species and tissues consumed by Greenlanders. In general, the levels of these are very low in terrestrial species and in muscle of many marine species. High organochlorines concentrations are typically found in blubber of marine mammals and high metal levels in liver and kidney of seals and whales. In this study, the mean intakes of cadmium, chlordanes and toxaphene significantly exceed ‘acceptable/tolerable intakes’ (ADI/TDI) by a factor between 2.5 and 6. Mean intakes of mercury, PCB and dieldrin also exceed ADI/TDI by up to approximately 50%. However as these figures are mean intakes and as variation in both food intake and contaminant levels is large, the variation of contaminant intake among individuals is also large, and some individuals will be exposed to significantly higher intakes. The mean intakes of DDT, HCH and chlorobenzenes are well below the ADI/TDI values, and it seems unlikely that the TDI for these contaminants normally is exceeded in the Greenland population. The evaluation of contaminant intake in this study points to seal muscle, seal liver, seal kidney, seal blubber and whale blubber as the dominant contributors of contaminants in the traditional diet. Levels in liver from Greenland halibut, snow crab, king eider, kittiwake, beluga and narwhal and kidney of beluga and narwhal are also high but were, with the exception of toxaphene in Greenland halibut liver, not important sources in this study, because they were eaten in low quantities. A way to minimize contaminant intake would be to avoid or limit the consumption of diet items with high contaminant levels. If we assume a traditional diet composition in this study without fish liver, bird liver, seal liver, seal kidney, seal blubber, whale liver, whale kidney and whale blubber, the intake of all contaminants would be below the TDIs for these. This will result in a reduction of the intake of the amount of traditional food of only 24–25%, and it is not likely that this changed diet will result in deficiency of minerals, vitamins or other nutritional compounds.

Metal- and Tissue-Dependent Relationship between Metallothionein mRNA and Protein

Metallothionein (MT) expression is transcriptionally regulated but recent evidence suggests that translation of MT mRNA may be regulated under some circumstances (Vasconcelos et al., Biochem. J., 315, 665–671, 1996). A systematic investigation of MT mRNA, protein, and metal levels in liver and kidney of cadmium- or copper-treated rats was made to further understand the relationship between mRNA and protein in particular. Adult rats were injected once with either Cd (8.9 μmol/kg) or Cu 2+ (8.7 μmol/kg) as the chloride salts, and the liver and kidney concentrations of MT-1 and MT-2 mRNA, total soluble MT protein, and tissue Cd, Cu, and Zn were monitored over 48–72 h. The metal composition in the soluble MT protein fraction was also analyzed by on-line size-exclusion chromatography-ICP/MS. Discrepancies between mRNA and protein levels were found in both tissues, but particularly in kidney. Cd treatment significantly increased renal MT-1 and MT-2 mRNA levels but protein was unaffected. In contrast, Cu actually decreased renal MT-1 and MT-2 mRNA but significantly increased MT protein. Cd induced considerably more MT-1 than MT-2 mRNA in liver, but induction of both isoforms was similar in kidney and in liver of Cu-treated rats. Changes in tissue metal levels tended to reflect MT protein levels and Cd appeared to bind to existing MT in the kidney. The results support the contention that MT protein levels often bear no clear relationship with mRNA levels and emphasizes the importance of measuring both in studies of MT expression.

Assessment of Tolerant Sunfish Populations (Lepomis sp.) Inhabiting Selenium-Laden Coal Ash Effluents: 2. Tissue Biochemistry Evaluation

Sunfish were collected from a fly ash pond-receiving stream and an Ohio River reference site to assess biochemical responses to coal ash effluent exposure. Selenium levels in sunfish from the receiving stream were higher than toxic thresholds associated with adverse population effects and reproductive impairment. Tissue biochemistry was found to be indicative of metal exposure and effect, but varied widely. Liver glycogen was positively correlated with increased liver metal levels, indicating no adverse effect upon stored carbohydrate levels. Lipid levels decreased with increasing metals, indicating possible nutritional stress. Protein levels increased with increasing metal levels, possibly due to the synthesis of proteins to sequester the metals. ATPase, dUTPase, and alkaline phosphatase activity generally decreased with exposure to ash pond metals, but remained within normal physiological ranges. Fish condition factors and liver somatic indices were correlated with liver lipid levels, dUTPase activity, and gill ATPase and alkaline phosphatase activity. Exposure to coal ash effluents produced biochemical markers of exposure that were associated with fish condition indicators; however, the indices themselves were not significantly affected by effluent exposure.

Effect of Acute Zinc Administration on Essential Metal Levels in Liver, Kidney, Lung and Heart of the Male Egyptian Toad Bufo Regularis

Effect of Acute Zinc Administration on Essential Metal Levels in Liver, Kidney, Lung and Heart of the Male Egyptian Toad Bufo Regularis

Assessment of various biomarkers in winter flounder from coastal Massachusetts, USA

AbstractSince 1992, the Massachusetts Water Resource Association has organized a Fish Day to assess the health of winter flounder in Boston Harbor and nearby areas. This report describes the levels of metal contaminants and selected biomarkers in flounder from Fish Day, 1996. Mean age for males and females was 3.5 years, which is lower than the age reported for fish collected during previous efforts. Body weight/body length ratios were significantly higher in females versus males. Liver Cd, As, Zn, and Cu, and muscle As were all elevated relative to U.S. Environmental Protection Agency designations for marine fish liver and muscle tissue in all animals from all sites. Male flounder from Boston Harbor had significantly higher liver Cd levels than female flounder from Cape Cod and Boston Harbor. Female flounder from Boston Harbor showed significantly less metallothionein (MT) protein and lower liver metal levels than those from Cape Cod. Metallothionein mRNA did not significantly differ between sites nor did MT protein or mRNA between males and females from Boston Harbor. Cytochrome P450 2E1 (CYP2E1)‐like and CYP1A1 activities were significantly higher at optimal temperatures than activity measured at field temperatures. No differences between groups were observed for either parameter at ambient temperatures, but at optimal temperature(s), Boston Harbor females had significantly higher CYP2E1‐like and CYP1A1 activities than Boston Harbor males. A negative correlation was found between maximal CYP1A1 activity and age for the Boston Harbor fish and a positive correlation for all fish between CYP2E1‐like activity at ambient temperature and percent liver lipid. No differences were observed for liver lipid and microsomal protein between any of the groups. Liver glycogen showed a sex‐dependent difference for the Boston Harbor group with levels in females significantly higher than males. These differences in contaminant levels and biomarkers are discussed within the context of data from previous Fish Days and the implications for flounder health within Boston Harbor.

Effects of Heavy Metals on Prey Abundance, Feeding Habits, and Metal Uptake of Brown Trout in the Arkansas River, Colorado

We examined the effects of heavy metals on prey abundance, feeding habits, and metal bioaccumulation of brown trout (Salmo trutta) at two sites in the Arkansas River, a Colorado stream polluted by mining discharges. We hypothesized that altered prey communities and exposure to metals would affect brown trout feeding habits, bioaccumulation, and condition. Prey communities at the upstream reference station (AR1) were dominated by metal-sensitive mayflies (Ephemeroptera) and black flies (Diptera: Simuliidae), whereas those at the downstream polluted station (AR5) were dominated by metal-tolerant chironomids (Diptera: Chironomidae) and caddisfiies (Trichoptera). Differences in prey community composition were reflected in the feeding habits of brown trout, which consumed greater numbers of chironomids and caddisflies at station AR5. Concentrations of heavy metals (Cd, Cu, and Zn) in water, dominant prey taxa, and brown trout stomach contents were greater at station AR5. Metal levels were also significantly elevated in brown trout gill and gut tissue at the downstream station, indicating greater metal exposure. However, in contrast to our predictions, metal levels in liver and kidney tissue, the primary organs of metal storage and regulation, were either similar at stations AR1 and AR5 or greater at the upstream station. In addition, brown trout size and condition factors (weight/length3) were significantly reduced at station AR1 compared with AR5. Condition factors were significantly correlated with metal levels in liver tissue at AR1 but not at AR5. We hypothesize that greater prey abundance and slightly warmer water temperature at the downstream station influenced fish condition and metal regulation in brown trout. These results demonstrate that bioaccumulation of metals by brown trout in the field is complex and influenced by several factors in addition to metal levels in food and water.