Showing papers on "Lead acetate published in 2002"

Tissue levels of lead in experimentally exposed zebra finches (Taeniopygia guttata) with particular attention on the use of feathers as biomonitors.

Abstract: We tested experimentally whether zebra finch feathers can be used as a biomonitor for lead pollution, and we examined whether lead exposure influences the accumulation of zinc into feathers. Two groups of eight adult male zebra finches were dosed with, respectively, 0 and 25 ppm lead as lead acetate in their drinking water. After 30 days, lead-treated zebra finches accumulated significantly higher lead concentrations in brain, fat, kidney, liver, muscle, testes, and regrown outer tail feathers than control individuals. Lead levels in regrown outer tail feathers were significantly higher than in original outer tail feathers in the exposed group. The concentration of lead in original (not regrown) fifth tail feathers at the end of the experiment was significantly higher than lead levels in the original outer tail feathers. Our results indicate that lead in regrown feathers originates both from internal deposition and external contamination through the excretion of the uropygial gland during preening. Lead levels in regrown feathers were significantly correlated with levels in liver, kidney, and muscle, suggesting that feathers can be used as a biomonitor for lead. We found that lead had an influence on the metabolism of zinc. Zinc concentrations in the regrown feathers were significantly lower in the lead-treated group although zinc levels in the liver did not differ significantly. Moreover, lead and zinc concentrations in the feathers were significantly negatively correlated.

Genotoxicity induced in CD-1 mice by inhaled lead: differential organ response.

Abstract: Lead is perhaps the longest used and best recognized toxic environmental chemical and it is still being used recklessly. Lead (Pb) has been found to be capable of eliciting a positive response in an extraordinarily wide range of biological and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA synthesis, mutation, chromosomal aberrations, cancer and birth defects. Since inhalation is one of the most important routes of environmental Pb exposure, in the present study a lead inhalation model in mice was implemented in order to detect the induction of genotoxic damage as single-strand breaks and alkali-labile sites in several mouse organs (nasal epithelial cells, lung, whole blood, liver, kidney, bone marrow, brain and testes), assessed by single cell gel electrophoresis (SCGE) or Comet assay. We found differences among the organs studied after a single and subsequent inhalations: in the organs analyzed we observed a positive induction of DNA damage after a single inhalation only in the liver and the lung. In subsequent inhalations the response was positive in all organs except the testicle, however, DNA damage induction over time was different for each organ. A correlation between length of exposure, DNA damage and metal tissue concentration was observed for lung, liver and kidney. Differences in DNA damage occurred in organs when lead acetate was administered acutely or sub-chronically. These results show that lead acetate inhalation induces systemic DNA damage but that some organs are special targets of this metal, such as lung and liver, depending in part on length of exposure, suggesting alternative organ processes to handle lead intoxication.

Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone system in the male rat.

Abstract: Lead is a male reproductive toxicant. Data suggest that rats dosed with relatively high levels of lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The current study evaluated whether exposure to low levels of lead acetate over longer periods of time would produce a similar pattern of adaptation to toxicity at the molecular and biologic levels. Adult 100-day-old Sprague-Dawley male rats were dosed with 0, 0.025, 0.05, 0.1, and 0.3% lead acetate in water. Animals were killed after 1, 4, 8, and 16 weeks of treatment. Luteinzing hormone (LH) and GnRH levels were measured in serum, and lead levels were quantified in whole blood. Hypothalamic GnRH mRNA levels were also quantified. We found no significant differences in serum LH and GnRH among the groups of animals treated within each time period. A significant dose-related increase of GnRH mRNA concentrations with lead dosing occurred in animals treated for 1 week. Animals treated for more than 1 week also exhibited a significant increase in GnRH mRNA, but with an attenuation of the increase at the higher concentrations of lead with increased duration of exposure. We conclude that the signals within and between the hypothalamus and pituitary gland appear to be disrupted by long-term, low-dose lead exposure.

Effect of lead and arsenic on murine macrophage response

Abstract: Splenic macrophages are highly efficient in trapping and concentrating foreign substances carried in the blood and also the major sites where antibodies are synthesised and from where they are released into the circulation. Lead and Arsenic as environmental agents are considered to be high priority toxic substances largely due to their carcinogenic potentials in humans. However, these heavy metals as carcinogens remain an enigma because while they are definitely active in humans, carcinogenesis in the rodent model has never been convincingly demonstrated. Although macrophages are predominantly recruited to the site of inflammation during inflammatory distress as well as in immune response, nothing is known about the interaction of lead and arsenic with macrophages and their possible role in immunotoxicologic effect. In the present study it is reported that in vivo lead acetate treatment (10 mg/kg body wt) inhibits the cell adhesion property and alters the cell morphology in the splenic macrophages...

Maturation-dependent neurotoxicity of lead acetate in vitro: implication of glial reactions.

Abstract: Despite a wealth of data on the neurotoxic effects of lead at the cellular and molecular levels, the reasons for its development-dependent neurotoxicity are still unclear. Here, the maturation-dependent effects of lead acetate were analyzed in immature and differentiated brain cells cultured in aggregates. Markers of general cytotoxicity as well as cell-type-specific markers of glial and neuronal cells showed that immature brain cells were more sensitive to lead than the differentiated counterparts, demonstrating that the development-dependent neurotoxicity of lead can be reproduced in aggregating brain cell cultures. After 10 days of treatment, astrocytes were found to be more affected by lead acetate than neurons in immature cultures, and microglial cells were strongly activated. Eleven days after cessation of the treatment, lead acetate caused a partial loss of astrocytes and an intense reactivity of the remaining ones. Furthermore, microglial cells expressed a macrophagic phenotype, and the loss of activity of neuron-specific enzymes was aggravated. In differentiated cultures, no reactive gliosis was found. It is hypothetized that the intense glial reactions (microgliosis and astrogliosis) observed in immature cultures contribute to the development-dependent neurotoxicity of lead.

Effect of lead exposure on the erythrocytic antioxidant levels in goats.

Abstract: Fifteen adult female goats were orally exposed to 5.46 mg lead (as lead acetate) per kg body weight daily for 2 weeks to study the antioxidant enzymes of the erythrocyte, lipid peroxide level, total thiol groups and total antioxidant status (TAS) in plasma. Ten goats served as unexposed control. Blood samples were collected before exposure (day 0) and on days 7 and 14. Ten per cent erythrocyte haemolysate was prepared and analysed for glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), total thiol groups and lipid peroxide. TAS was determined in plasma. There was a significant (P < 0.05) increase of erythrocytic GPx, SOD, CAT, total thiol groups and TAS on day 7 which was followed by a significant (P < 0.05) decrease of all these parameters on day 14. Lipid peroxide level increased significantly (P < 0.05) and the maximum level was attained by day 14. The results obtained indicate a possible role of free radicals in lead poisoning pathogenicity.

Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney.

Abstract: The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-α-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p) and DMSA (20 mg/kg body weight per day i.p) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of γ-glutamyl transferase and N-acetyl β-D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione-S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell.

Effects of combined exposure to lead and cadmium on pituitary membrane of female rats.

Abstract: The effects of combined exposure to lead and cadmium on pituitary membrane were studied. Adult female rats were treated intraperitoneally with either lead acetate and cadmium acetate alone or in combination at a dose of 0.05 mg/kg daily for 15 days. Both metals accumulated in the pituitary after the exposure. The membrane fluidity was decreased after the heavy-metal treatment. Among the three groups cadmium treatment showed more effect than did other treatments and the combined treatment showed intermediate values. Na+K+ATPase activity was decreased significantly by cadmium and combined treatments. The Schiff's base and inorganic peroxide levels were increased after the metal exposure. In conclusion, exposure to lead and cadmium caused accumulation of the metals in the pituitary and lowered the membrane fluidity, which may affect membrane function and cause alterations in receptor binding and secretory mechanism(s) of pituitary hormones. The combined treatment with metals produced intermediate results.

The protective effect of calcium against genotoxicity of lead acetate administration on bone marrow and spermatocyte cells of mice in vivo.

Abstract: The protective effect of calcium given orally by gavage with two doses (40 and 80 mg/kg body weight) was evaluated against clastogenecity induced by lead acetate with two concentrations (200 and 400 mg/kg diet) on bone marrow and spermatocyte cells of mice in vivo. The parameter screened was percentage of chromosomal aberrations with and without gaps and sperm abnormalities. Statistical analyses indicated the protection efficacy of calcium with the high dose rather than the other in both types of mouse cells. The observation from the laboratory tests, dealing that lead acetate can be considered as an environmental genotoxic material. We recommended that it must be administered of calcium (as calcium chloride) as a protective agent to reduce the genotoxic effect of lead in the somatic and germ cells.

Lead exposure enhances virus multiplication and pathogenesis in mice.

Abstract: Suppression of the immune system by environmental xenobiotics may cause increased susceptibility of the host towards a variety of microbial pathogens an result in a life-threatening state We investigated whether lead exposure would enhance susceptibility to Semliki Forest Virus (SFV) Mice orally exposed to lead acetate (625, 125, 250 or 500 mg/kg bw) exhibited increased mortality and decreased mean survival time compared to untreated animals on challenge with SFV The mortality was associated with enhancement of high virus titer and earlier appearance of virus in lead-exposed mice Histopathological studies observed enhancement of viral pathogenesis in a dose dependent pattern in the lead-dosed group challenged with SFV The results indicate that exposure to lead enhanced susceptibility to viral infection Environmental metal contamination and subsequent infection by pathogenic microbes points necessitate studies on the interaction of environmental pollutants on the immune system

Lead stimulates the glutathione system in selective regions of rat brain.

Abstract: Lead (Pb) is a highly neurotoxic agent that causes functional and structural abnormalities in the brain. Glutathione (GSH) is a main molecule involved in the protection mechanisms against Pb itself and against reactive oxygen species generated by the metal. This study was carried out to investigate the effect of Pb on the glutathione system in several regions of adult rat brain. In the model of Pb toxicity, adult Wistar rats were exposed to 25 mg of lead acetate/kg b.w. for 3 days. Glutathione and the related enzymes i.e. g-glutamylcysteine synthetase (g-GCS), glutathione reductase (GR) and glutathione S-transferases (GSTs) were examined in the hippocampus, cerebellum and forebrain. In the cytosolic fraction the concentration of total GSH and the activity of GR increased only in the cerebellum of Pb-exposed rats. Higher increases of both parameters were observed in mitochondrial fraction obtained from the cerebellum and hippocampus. The activity of cytosolic enzyme - g-GCS was enhanced only in the forebrain. Regarding cytosolic GSTs, changes in the activity together with enhanced relative density of enzyme protein were found in the cerebellum and hippocampus. Generally, activation of the glutathione system observed shortly after Pb treatment suggests the protective response of the brain to toxic insult. Regional differences in the pattern of these changes may coincide with different susceptibility to Pb. Present results suggest also that mitochondrial mechanisms might account for lead toxicity.

Effect of low level exposure of lead and cadmium on hepatic estradiol metabolism in female rats.

Abstract: Toxic effect of metal cations on female reproduction and gonadal functions was studied. Adult synchronized female rats were treated intraperitoneally with lead acetate and cadmium acetate separately and in combination (0.025, 0.05 and 0.1 mg/kg body wt) for 15 days. The metabolizing enzymes (17beta-hydroxy steroid oxidoreductase and UDP glucoronyl transferase) activities decreased with increasing dose showing significant change compared to control. Also, significant decrease in cytochrome P450 (CYP450) content was found after the treatment. Displacement of zinc bound to metallothionein was more in cadmium treated rats compared to other groups. In all these parameters, treatment in combination of lead and cadmium showed intermediate results indicating some kind of competition between the two metals. But the histological studies showed that combined treatment caused more cytotoxic effect than cadmium and lead alone. These results indicated that metal cations tested did have a direct inhibitory effect on metabolizing enzyme activities.

Concentration dependency in lead-inhibited steroidogenesis in MA-10 mouse Leydig tumor cells.

Abstract: Lead acetate (Pb) decreases the expression of steroidogenic acute regulatory (StAR) protein and the enzymatic activities of cytochrome P-450 side-chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in a concentration-dependent manner in Leydig cells at 2 h, the duration of submaximal inhibition. This study was undertaken at 3 h of Pb incubation to compare the effects at maximal metal inhibition of steroidogenesis. Quantitatively a 3-h Pb incubation with MA-10 cells resulted in higher decreases in human chorionic gonadotropin (hCG)-stimulated progesterone production, expression of StAR protein, and the activity of 3beta-HSD compared to 2 h. In contrast, lead inhibited dibutyryl cAMP (dbcAMP)-stimulated progesterone production but lacked this effect at 2 h. Surprisingly, Pb at 3 h of incubation did not affect P450scc enzyme activity, yet this enzymatic activity was inhibited at 2 h. Data indicate that incubation time is a factor in Pb-induced alterations in MA- 10 cell steroidogenesis.

Influence of age on lead-induced oxidative stress in rat

Abstract: Influence of age on lead-induced oxidative stress was investigated in young, adult, and old rats maintained on 0.2% lead acetate (2000 ppm lead) in drinking water for 3 mo. The lead-induced depletion of blood and liver reduced glutathione was about equal in young and adult but not in old rats. The increases in blood, liver, and brain oxidized glutathione and blood and liver superoxide dismutase levels were related to the accumulation of lead in these tissues and followed the order young >adult>old. The lead-induced inhibition of blood δ-aminolevulinic acid dehydratase activity, lowering in hemoglobin, and enhanced urinary excretion of δ-aminolevulinic acid were independent of variation in age. The results indicate that young rats may be most sensitive, whereas old rats may be most resistant to some of the oxidative effects of lead examined, which may be related to the accumulation of lead.

[Effect of lead acetate on the apoptosis and the expression of bcl-2 and bax genes in rat brain cells].

Abstract: OBJECTIVES To explore the effect of lead acetate on the apoptosis of rat brain neural cells and the relationship between the apoptosis and the bcl-2 as well as bax gene expression METHODS Lead acetate was given to SD rats by intraperitoneal injection for 5 days at the dosage of 25, 50 and l00 mg/kg body weight respectively The rates of apoptosis and the expression of bcl-2 (Bcl-2) and bax (Bax) in neural cells from cerebral cortex, hippocampus and carebellum were measured respectively by flow cytometry (FCM) RESULTS The rates of apoptosis in neural cells from cerebral cortex, hippocampus and cerebellum in every treatment group were significantly higher than that of control (P < 001), and there was a significant dose-response relationship (r = 0998, 0989 and 0997 respectively) The expression of bcl-2 was significantly decreased, whereas bax was significantly increased, in neural cells from cerebral cortex, hippocampus and cerebellum in every lead acetate treatment group (FI) compared with the control group, and there was a significant dose-response relationship (r = -0886, -0787 and -0832 respectively for bcl-2, r = 0971, 0988 and 0991 respectively for bax) The value of Bcl-2/Bax in every treatment group decreased significantly compared with control, and there was a nice dose-response relationship (r = -0863, -0829 and -0999, respectively) Correlation analysis showed that rates of apoptosis were inversely correlated with the expression of bcl-2 (r = -0750, -0509, and -0667, respectively), whereas positively correlated with the expression of bax (r = 0748, 056l, and 0668, respectively) And there were inverse correlations between the rates of apoptosis and Bcl-2/Bax expression CONCLUSION Lead may induce apoptosis in rat brain neural cells through the down regulation of bcl-2 and the up regulation of bax gene expression

A stereological analysis of renal glomeruli following chronic Lead intoxication in rat during a continuous period of 8 weeks

Abstract: Stereologic methods are used to abtain quantitative information about 3-dimensional structures from histologic sections. The aim of the present study was using new and unbiased stereologic techniques to investigate changes in volume and number of glomeruli after chronic lead acetate intoxication both quantitatively and in 3-dimensional spaces.Lead is one of the heavy metals that has adverse effects on renal function. These effects may involve the renal tubules as well as the glomeruli. Several qualitative histologic studies have been performed regarding the effects of lead on renal tissue and the glomeruli some of which report changes in volume and number of the glomeruli.Male adult wistar rats in four groups (each including 9 rats) were randomly selected. The case groups (treatment groups) were first given 0.5% and then 1% lead acetate in their drining water for 8 weeks. The negative and positive control groups were given distilled water and 0.4% acetic acid solution in the same period respectively.Stereologic analysis was performed based on Cavalierie’s principle to determine the reference volume (VReference), the fraction volume of glomeruli (VVGlom), and total glomerular volume (VTGlom). Furthermore the numerical density (NVGlom) and total number of glomeruli (NTGlom) were estimated using the physical dissector.Results showed that the number of glomeruli in case group which had received 1% lead acetate in drinking water decreased significantly (P 0. This study confirms qualitative observational histologic studies with an unbiased and exact method, and expresses the chages in the number and volume of renal glomeruli after lead intoxication.05). on the other hand, glomerular total volume in both 1% and 0.5% groups increased significantly after lead intoxication. Comparing positive and negative control groups (P<0.01

Histochemical Demonstration of the Alterations in the Renal Dehydrogenases Activities Induced by Lead in Wistar Albino Rats ( Rattus norvegicus)

Abstract: A total of 112 male albino rats (Rattus norvegicus) were divided into seven groups and exposed to lead acetate trihydrate (0, 0.125, 0.25, 0.5, 1.0, 2.0 and 4 per cent for 1 to 8 months) in drinking water to investigate possible histochemical changes of nine renal dehydrogenases due to lead intoxication. A marked increase in the activity of lactate-, glucose-6-phosphate-, α-glycerophosphate-, reduced nicotinamide adenine dinucleotide (NAD)- and reduced nicotinamide adenine dinucleotide phosphate (NADP) dehydrogenase was observed while significant reduction was recorded in the activity of succinate-, malate-, isocitrate- and glutamate dehydrogenase. Changes in the activity of renal dehydrogenases were seen mainly in the pars recta and to a lesser extent in the pars convoluta and the ascending thick segment of the loop of Henle while the other medullary portions of the renal tubule were less affected. These histochemical findings led us to conclude that such changes in the renal dehydrogenases activities were due to chronic lead exposure and could be an adaptation to the metabolic, structural and functional alterations in the organelles of the renal cells especially the mitochondria.

Combined effect of lead and cadmium on lipid peroxidation in renal tubular epithelial cells of rats

Abstract: In order to observe the combined effects of lead and cadmium on lipid peroxidation, the cultured renal tubular epithelial cells (TEC) of rats are used to perform 3 x 3 factorial experimental design. In the experimental group (A-H), rats are given lead and cadmium respectively for 6 hours at different concentrations (A: lead acetate 0.02 mmol/L; B: lead acetate 0.1 mmol/L; C: cadmium chloride 0.001 mmol/L; D: cadmium chloride 0.004 mmol/L; E: lead acetate 0.02 mmol/L + cadmium chloride 0.001 mmol/L; F: lead acetate 0.02 mmol/L + cadmium chloride 0.004 mmol/L; G: lead acetate 0.1 mmol/L + cadmium chloride 0.001 mmol/L; H: lead acetate 0.1 mmol/L + cadmium chloride 0.004 mmol/L). After TEC are smashed by supersonic, the concentrations of glutathione (GSH) and malondiadehyde (MDA) in cells are analyzed. The same analysis is also done for the determination of the activity of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). In comparison with control group, significant decrease in activities of GSH, GSH-Px, SOD in cells treated with lead and cadmium and increases of MDA are observed. The data from ANOVA analysis show that the interaction between lead and cadmium on GSH, MDA, and SOD in TEC (P < 0.05) is demonstrated while no interaction on GSH-Px is shown.

[The effect of anthocyanins from Aronii melanocarpa and acetylcysteine on selected after-effects of lead acetate poisoning].

Abstract: In recent years we have widely examined the results of protracted exposures on lead. Lead mostly shows that it accumulates in bones in an insoluble phosphate form. In much of the experimental research we observed that lead can cause reactive forms of oxygen and oxidative stress. The examination was carried out on 40 female and male Wistar rats weighing 200-250 g. They lived in the animal quarters with a stable temperature and humidity. They were fed with standard fodder (Murigan) and water ad libitum. In the work carried out the effect of anthocyanins of Aronia Melanocarpa Elliot and acetylcysteine on the selected parameters of oxidative stress of experimental animals with chronic lead acetate poisoning were examined. After administration anthocyanins substantially decreased the concentration of unsaturated fatty acid peroxidation and carbonyls in blood serum. At the same time we observed a significant decrease of 8-hydroxy-2'-deoxyguanosine in urine. Antocyanins from Aronia Melanocarpa appear to be a good substance for the diminishing of oxidative stress, these results caused with long-term administration of lead acetate.