Postnatal lead poisoning impairs behavioral recovery following brain damage

Neurotoxicology. 2007 Aug 16; [Epub ahead of print]

Postnatal lead poisoning impairs behavioral recovery following brain damage.

Schneider JS, Decamp E.

Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States.

Lead is a potent environmental toxicant with well-known effects on intelligence, school achievement and behavior. Lead exposure is also associated with an increased risk of a variety of health problems including cancer, hypertension, cardiovascular disease, and renal disease. Considering the risk of hypertension, cardiovascular problems, and stroke following lead exposure, the current research assessed the extent to which postnatal exposure to environmentally relevant levels of lead could impair the recovery from a later occurring brain injury. Using a photochemical thrombotic stroke model we found that postnatal lead exposure significantly impaired post-stroke recovery of beam walking ability and proprioceptive limb placing. Considering the increased risk for hypertension and cardiovascular disease in lead-exposed humans, diminished capacity for repair or adaptation following lead exposure needs to now be examined in greater detail.

PMID: 17707511 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17707511&itool=iconabstr&itool=pubmed_DocSum

Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on methylmercury-induced locomotor deficits and cerebellar toxicity in mice

Toxicology. 2007 Jul 13; [Epub ahead of print]

Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on methylmercury-induced locomotor deficits and cerebellar toxicity in mice.

Carvalho MC, Franco JL, Ghizoni H, Kobus K, Nazari EM, Rocha JB, Nogueira CW, Dafre AL, Müller YM, Farina M.

Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Ciências Naturais, Centro de Ciências Naturais e Exatas, Fundação Universidade Regional de Blumenau, Blumenau, SC, Brazil.

Chelating therapy has been reported as a useful approach for counteracting mercurial toxicity. Moreover, 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, was found to increase urinary mercury excretion and decrease mercury content in rat brain after methylmercury (MeHg) exposure. We evaluated the capability of DMPS to reduce MeHg-induced motor impairment and cerebellar toxicity in adult mice. Animals were exposed to MeHg (40mg/L in drinking water, ad libitum) during 17 days. In the last 3 days of exposure (days 15-17), animals received DMPS injections (150mg/kg, i.p.; once a day) in order to reverse MeHg-induced neurotoxicity. Twenty-four hours after the last injection (day 18), behavioral tests related to the motor function (open field and rotarod tasks) and biochemical analyses on oxidative stress-related parameters (cerebellar glutathione, protein thiol and malondyaldehyde levels, glutathione peroxidase and glutathione reductase activities) were carried out. Histological analyses for quantifying cellular damage and mercury deposition in the cerebellum were also performed. MeHg exposure induced a significant motor deficit, observed as decreased locomotor activity in the open field and decreased falling latency in the rotarod apparatus. DMPS treatment displayed an ameliorative effect toward such behavioral parameters. Cerebellar glutathione and protein thiol levels were not changed by MeHg or DMPS treatment. Conversely, the levels of cerebellar thiobarbituric acid reactive substances (TBARS), a marker for lipid peroxidation, were increased in MeHg-exposed mice and DMPS administration minimized such phenomenon. Cerebellar glutathione peroxidase activity was decreased in the MeHg-exposed animals, but DMPS treatment did not prevent such event. Histological analyses showed a reduced number of cerebellar Purkinje cells in MeHg-treated mice and this phenomenon was completely reversed by DMPS treatment. A marked mercury deposition in the cerebellar cortex was observed in MeHg-exposed animals (granular layer>Purkinje cells>molecular layer) and DMPS treatment displayed a significant ameliorative effect toward these phenomena. These findings indicate that DMPS displays beneficial effects on reversing MeHg-induced motor deficits and cerebellar damage in mice. Histological analyses indicate that these phenomena are related to its capability of removing mercury from cerebellar cortex.

PMID: 17703864 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17703864&itool=iconabstr&itool=pubmed_DocSum

Scalp hair as a biomarker in environmental and occupational mercury exposed populations: Suitable or not.

1: Environ Res. 2007 Aug 10; [Epub ahead of print]

Scalp hair as a biomarker in environmental and occupational mercury exposed populations: Suitable or not.

Li YF, Chen C, Li B, Wang J, Gao Y, Zhao Y, Chai Z.

Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; Graduate University of the Chinese Academy of Sciences, Beijing 100049, China.

Hair is a well-established and widely used matrix for measuring mercury exposure of an individual. Although a variety of washing procedures to remove external mercury contamination have been proposed, no standardized procedures are available yet. In this study, different washing reagents like l-cysteine (Cys), 2-mercaptoethanol (ME), and disodium diaminoethanetetra acetate (EDTA) were used to find out if it is possible to remove mercury contamination from human scalp hair spiked with HgCl(2) solutions at different concentrations. It was found that the external mercury contamination could not be fully washed off even using reagents with high affinity to mercury like l-cysteine and ME. However, for the well-pulverized CRM hair samples some of the endogenous mercury was washed off. It suggests that hair is not a suitable biomarker for evaluation of total mercury exposure especially in people like mercury miners or gold miners/burners associated with serious external Hg exposure. However, hair still can be used as an indicator for methyl mercury exposure because, generally, there is almost no exogenous contamination of methyl mercury in hair.

PMID: 17706190 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17706190&itool=iconabstr&itool=pubmed_DocSum

Glutathione level after long-term occupational elemental mercury exposure

1: Environ Res. 2007 Aug 14; [Epub ahead of print]

Glutathione level after long-term occupational elemental mercury exposure.

Kobal AB, Prezelj M, Horvat M, Krsnik M, Gibicar D, Osredkar J.

University Medical Centre Ljubljana, Institute of Clinical Chemistry and Biochemistry, Njegoseva 4, SI-1525 Ljubljana, Slovenia.

Many in vitro and in vivo studies have elucidated the interaction of inorganic mercury (Hg) and glutathione. However, human studies are limited. In this study, we investigated the potential effects of remote long-term intermittent occupational elemental Hg vapour (Hg degrees ) exposure on erythrocyte glutathione levels and some antioxidative enzyme activities in ex-mercury miners in the period after exposure. The study included 49 ex-mercury miners divided into subgroups of 28 still active, Hg degrees -not-exposed miners and 21 elderly retired miners, and 41 controls, age-matched to the miners subgroup. The control workers were taken from "mercury-free works". Reduced glutathione (GSH) and oxidized disulphide glutathione (GSSG) concentrations in haemolysed erythrocytes were determined by capillary electrophoresis, while total glutathione (total GSH) and the GSH/GSSG ratio were calculated from the determined values. Catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in erythrocytes were measured using commercially available reagent kits, while urine Hg (U-Hg) concentrations were determined by cold vapour atomic absorption (CVAAS). No correlation of present U-Hg levels, GSH, GSSG, and antioxidative enzymes with remote occupational biological exposure indices were found. The mean CAT activity in miners and retired miners was significantly higher (p<0.05) than in the controls. No differences in mean GPx activity among the three groups were found, whereas the mean GR activity was significantly higher (p<0.05) in miners than in retired miners. The mean concentrations of GSH (mmol/g Hb) in miners (13.03+/-3.71) were significantly higher (p<0.05) than in the control group (11.68+/-2.66). No differences in mean total GSH, GSSG levels, and GSH/GSSG ratio between miners and controls were found. A positive correlation between GSSG and present U-Hg excretion (r=0.41, p=0.001) in the whole group of ex-mercury miners was observed. The significantly lower GSH level (p<0.05) determined in the group of retired miners (9.64+/-1.45) seems to be age-related (r=-0.39, p=0.001). Thus, the moderate but significantly increased GSH level, GR and CAT activity in erythrocytes in the subgroup of miners observed in the period after exposure to Hg degrees could be an inductive and additive response to maintain the balance between GSH and antioxidative enzymes in interaction with the Hg body burden accumulated during remote occupational exposure, which does not represent a severely increased oxidative stress.

PMID: 17706633 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17706633&itool=iconabstr&itool=pubmed_DocSum

Occupational aluminum exposure: Evidence in support of its neurobehavioral impact

Neurotoxicology. 2007 Jul 7; [Epub ahead of print] Links

Occupational aluminum exposure: Evidence in support of its neurobehavioral impact.

Meyer-Baron M, Schäper M, Knapp G, van Thriel C.

Leibniz Research Centre for Working Environment and Human Factors, Ardeystr. 67, 44139 Dortmund, Germany.

Aluminum is a metal with known neurotoxic properties which are linked to encephalopathy and neurodegenerative diseases. The objectives of the current meta-analysis study were: (1) to summarize neurobehavioral data obtained by epidemiological studies in occupational settings and (2) to analyze confounding within these data. The meta-analysis was based on estimates of effect sizes. Overall effect sizes were obtained by application of a random effects model. The final sample consisted of nine studies examining 449 exposed and 315 control subjects. The mean urinary aluminum concentrations in the exposed groups ranged from 13 to 133mug/l. Six neuropsychological tests, which yielded 10 performance variables, were analyzed. Nine overall effect sizes indicated an inferior performance for the exposed group. A significant overall effect size (d(RE)=-0.43) was obtained for the digit symbol test measuring speed-related components of cognitive and motor performance. Moreover, the individual effect sizes obtained for this test suggested an exposure-response relationship. Results obtained from either raw or adjusted mean scores revealed that confounding in the data could not be excluded. The results were compared to studies not included here due to a shortage of required data. Similarities were discussed in terms of sensitivity of the tests for detecting aluminum-related changes in brain function. There was concurring evidence from different studies that urinary Al concentrations below 135mug/l have an impact on cognitive performance. The significant effect for the digit symbol might be related to its multifaceted character which requires functioning in different components of cognitive and motor performance. This feature could possibly turn the test into a screening instrument for neurobehavioral effects. However, additional studies are necessary to verify and to differentiate the effect of aluminum on cognitive performance. From a neuropsychological perspective, implicit and explicit memory, visuo-spatial and central odor processing should be examined. A measure of verbal intelligence should be included in order to address the influence of confounding. Internationally standardized exposure measures would enhance the comparability of studies.

PMID: 17692380 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17692380&itool=iconabstr&itool=pubmed_DocSum

Immunosuppressive Effect of Subchronic Exposure to a Mixture of Eight Heavy Metals

Arch Environ Contam Toxicol. 2007 Jul 26; [Epub ahead of print]

Immunosuppressive Effect of Subchronic Exposure to a Mixture of Eight Heavy Metals, Found as Groundwater Contaminants in Different Areas of India, Through Drinking Water in Male Rats.

Jadhav SH, Sarkar SN, Ram GC, Tripathi HC.

Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122, Uttar Pradesh, India, snsarkar@ivri.up.nic.in.

Immunotoxicity is an important health hazard of heavy metal exposure. Because the risk of combined exposure in the population cannot be neglected, we examined whether subchronic exposure to a mixture of metals (arsenic, cadmium, lead, mercury, chromium, nickel, manganese, and iron) via drinking water at contemporary Indian groundwater contamination levels and at concentrations equivalent to the WHO maximum permissible limit (MPL) in drinking water can induce immunotoxicity in male rats. Data on groundwater contamination with metals in India were collected from literature and metals were selected on the basis of their frequency of occurrence and contamination level above the MPL. Male albino Wistar rats were exposed to the mixture at 0, 1, 10, and 100 times the mode concentrations (the most frequently occurring concentration) of the individual metals in drinking water for 90 days. In addition, one group was exposed to the mixture at a concentration equal to the MPL of the individual metal and another group was used as positive control for immune response studies. The end points assessed were weights of organs, hematological indices, humoral and cell-mediated immune responses, and histopathology of skin and spleen. The MPL and 1x doses did not significantly affect any of the parameters and none of the doses induced any significant changes after 30 days of exposure. The mixture at 10x and 100x doses increased the relative weight of the spleen, but that of thymus, adrenals, and popliteal lymphnodes were increased with the 100x dose. After 90 days, 10x and 100x doses decreased serum protein and globulin contents and increased the albumin:globulin ratio; the albumin level was decreased only with the 100x dose. After 60 days, the total erythrocyte count (TEC), hemoglobin (Hb) level, and packed cell volume (PCV) were decreased with the 100x dose, whereas after 90 days, 10x and 100x doses reduced the TEC, total leukocyte count, Hb level, PCV, mean corpuscular volume, and mean corpuscular hemoglobin. With the 100x dose, the lymphocyte count was decreased after 60 and 90 days, but the neutrophil number was increased after 90 days. Antibody titer was decreased after 75 days with the 100x dose, but after 90 days, it was decreased with both the 10x and 100x doses. In delayed-type hypersensitivity response, these two doses decreased ear thickness after 24 and 48 h and skin biopsies showed a dose-dependent decrease in inflammatory changes. Histologically, the spleen revealed depletion of lymphoid cells and atrophic follicles with reduced follicular activity with higher doses. The findings suggest that hematopoietic and immune systems are toxicologically sensitive to the mixture, which could lead to anemia and suppression of humoral and cell-mediated immune responses in male rats at 10 and 100 times the mode concentrations of the individual components in contaminated groundwater.

PMID: 17657459 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17657459&itool=iconabstr&itool=pubmed_DocSum