Showing papers on "Lead acetate published in 2003"

Protective effect of Spirulina on lead induced deleterious changes in the lipid peroxidation and endogenous antioxidants in rats.

Abstract: The present study aims to investigate the protective effect of Spirulina on lead-induced changes in the levels of lipid peroxidation and endogenous antioxidants in liver, lung, heart, kidney and brain of rats. Levels of elemental lead were also measured in the organs of rats in all experimental groups. In the liver, lung, heart and kidney of lead-exposed animals, there was a significant (p < 0.001) increase in the lipid peroxidation and a decrease in the levels of endogenous antioxidants. Although, Spirulina did not affect the deposition of lead in organs apart from the brain, simultaneous administration of Spirulina to lead exposed animals significantly (p < 0.001) inhibited lipid peroxidation and restored the levels of endogenous antioxidants to normal. To conclude, Spirulina had a significant effect on scavenging free radicals, thereby protecting the organs from damage caused by the exposure to lead. Further more, Spirulina showed a significant (p < 0.05) decrease in the deposition of lead in the brain.

In vitro genotoxicity of lead acetate: induction of single and double DNA strand breaks and DNA-protein cross-links.

Abstract: Lead is present in the natural and occupational environment and is reported to interact with DNA, but the mechanism of this interaction is not fully understood. Using the alkaline comet assay we showed that lead acetate at 1–100 μM induced DNA damage in isolated human lymphocytes measured the change in the comet tail length. At 1 and 10 μM we observed an increase in the tail length, whereas at 100 μM a decrease was seen. The former effect could follow from the induction of DNA strand breaks and/or alkali-labile sites (ALS), the latter from the formation of DNA–DNA and/or DNA–protein cross-links. No difference was observed between tail length for the alkaline and pH 12.1 versions of the assay, which indicates that strand breaks and not ALS are responsible for the tail length increase induced by lead. The neutral version of the test revealed that lead acetate induced DNA double-strand breaks at all concentrations tested. The presence of spin traps, 5,5-dimethyl-pyrroline N-oxide (DMPO) and N-tert-butyl-α-phenylnitrone (PBN) did not influence the level of DNA damage induced by lead. Post-treatment of the lead-damaged DNA (at 100 μM treatment concentration) by endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing oxidized DNA bases, as well as 3-methyladenine-DNA glycosylase II, an enzyme recognizing alkylated bases, gave rise to a significant increase in the extent of DNA damage. Proteinase K caused an increase in comet tail length, suggesting that lead acetate might cross-link DNA with nuclear proteins. Vitamin A, E, C, calcium chloride and zinc chloride acted synergistically on DNA damage evoked by lead. The results obtained suggest that lead acetate may induce single-strand breaks (SSB) and double-strand breaks (DSB) in DNA as well as DNA–protein cross-links. The participation of free radicals in DNA-damaging potential of lead is not important and it concerns other reactive species than could be trapped by DMPO or PBN.

Lead Acetate Induced Cytotoxicity in Male Germinal Cells of Swiss Mice

Abstract: Single intraperitoneal injection of lead acetate (200 mg/kg b.w) to Swiss mice stimulated testicular weight loss with a constant increase in the incidence of abnormal sperm population and decrease in the total sperm count. Testicular ascorbic acid also declined significantly during the post-treatment phase with significant rise in Lipid Peroxidation Potential (LPP) of the tissue. Elevated LPP is indicative of oxidative stress in treated mice testes. The possible role of lead-induced oxidative stress in culminating increased sperm abnormality and decreased sperm count have been discussed. Further, possible antioxidative role of testicular ascorbic acid in minimizing oxidative stress in lead- treated mice has been demonstrated.

Behavioral effects of chronic exposure to low levels of lead in Drosophila melanogaster.

Abstract: Through human activity lead has become a serious environmental neurotoxin, known to affect activity levels, attention and both sensory and cognitive function in children. Study of lead would be facilitated by having a model system that could be manipulated easily and quickly. We find Drosophila melanogaster ideal as such, and we have been studying effects of lead on courtship, fecundity and locomotor activity. We raised Canton-S flies from eggs to adult day 6–7 on medium made with lead acetate solution (2–100 μg/g), or with distilled water, and we measured adult body lead burdens by means of Inductively Coupled Plasma Mass Spectrometry (ICP-MS). To measure courtship effectiveness, five virgin females and five virgin males were transferred into an empty vial and the number of females that mated within 20 min was recorded. To measure fecundity, all adult offspring from eggs produced by one female within 12 days of mating were counted. To measure locomotor activity, individual flies were transferred to a grid-labeled petri dish and the number of lines crossed in 30 s was counted. The number of females mating within 20 min was increased significantly by exposure to 2 or 8 μg/g lead, and was decreased significantly by exposure to 20 or 50 μg/g lead. Fecundity was increased significantly by exposure to 2 μg/g lead, but was unaffected by exposure to 20 μg/g lead. Locomotor activity was consistently higher for males than for females, and was significantly reduced only by exposure to 50 μg/g lead, and then only for males. We thus defined for Drosophila a lowest observable effect level (LOEL) of 2 μg/g lead, which is considerably lower than the doses shown previously to affect this animal. The dose–response curve was biphasic for the number of females mating within 20 min, an example of hormesis , a non-linear response that has been reported for low levels of stressors as diverse as pollutants and radiation. We hope from further studies with Drosophila to understand better how lead affects the developing nervous system, and thus ultimately its effects on children.

Prophylactic effect of melatonin in reducing lead-induced neurotoxicity in the rat.

Abstract: Oxidative stress is a likely molecular mechanism in lead neurotoxicity. Considering the antioxidant properties of melatonin, this study investigated the neuroprotective potential of melatonin in the hippocampus and corpus striatum of rats treated with lead. Three groups of male rats (control, lead acetate-treated [100 mg/kg], and lead acetate plus melatonin [10 mg/kg] for 21 consecutive days) were used. Levels of products of lipid peroxidation (LPO), glutathione (GSH) and superoxide dismutase (SOD) activity were measured in brain homogenates. Histological changes in the pyramidal cells of the hippocampus and the putamen of the corpus striatum were examined. The results documented increased LPO and decreased GSH and SOD activity in the brain homogenates of lead-treated rats. Histological observations revealed severe damage and a reduction in neuronal density in the hippocampus and corpus striatum. When melatonin was given to lead-treated rats, it almost completely attenuated the increase in LPO products and restored GSH levels and SOD activity. Also, the morphological damage was reduced and neuronal density was restored by melatonin. Considering the ease with which melatonin enters the brain, these results, along with previous observations, suggest that melatonin may be useful in combating free radical-induced neuronal injury that is a result of lead toxicity.

Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva.

Abstract: The role of oxidative stress in lead toxicity has been proposed in many organs, however, no study has been performed in the salivary glands, which are important parts of the gastrointestinal tract with a high implication in health of the whole body. Recently, it has been proposed that increasing the levels of cGMP and cAMP in the cells may protect from the neurotoxicity of lead. The objective of this study was to determine the ability of lead acetate to produce oxidative stress in rat submandibular as the main salivary gland of the body and to study the role of pretreatment by specific phosphodiesterase inhibitors in the prevention of oxidative stress. Lead acetate (100 mg/kg), alone or in combination with theophylline (25 mg/kg) and sildenafil (5 mg/kg), was administered intraperitoneally to rats. After 2 hours and under general anaesthesia, the submandibular gland ducts were cannulated intraorally using microcannula, and pure saliva was collected for 30 min using pilocarpine (8 mg/kg) as a secretagogue. The submandibular glands were then isolated free under surgery. Oxidative stress in the gland and pure saliva were evaluated measuring lipid peroxidation (thiobarbituric acid reactive substances assay), total thiol groups content and total antioxidant capacity (the ferric reducing ability assay). Results showed significant oxidative stress in the gland and secretions as indicated by increased lipid peroxidation, decreased total antioxidant capacity and thiol group levels. The use of cAMP and cGMP phosodiesterase inhibitors, theophylline and sildenafil, prevented lead-induced increased lipid peroxidation and also protected from decreased thiol groups content and total antioxidant power of the gland and secretions. The same trend of effects was observed in gland and saliva. It is concluded that lead toxicity is mediated through oxidative stress in salivary glands, while increasing intracellular cAMP and cGMP levels may prevent lead-induced oxidative stress.

Biochemical and ultrastructural evidences for toxicity of lead through free radicals in rat brain.

Abstract: Studies suggest that some lead-induced toxic effects may occur through free radical production and oxidative stress. This study examined the relationship between brain histopathological alterations and oxidative stress in subchronic lead exposure. Male Albino rats received lead acetate at 0.01%, 0.05% and 0.1% w/v in their drinking water for 30 days. Animals given sodium acetate (0.1% w/v) served as control in the same period. At the end of exposure, blood-lead levels, blood catalase (CAT) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content (in blood and brain) were measured. The brain tissue samples were prepared and analysed by light and scanning electron microscopy. The results show that, the blood-lead levels in treated animals were higher in comparison with control. CAT and SOD activities in animals treated with 0.01% and 0.05% w/v did not increase in comparison with control (P > 0.05) but these values were higher in animals treated with 0.1% w/v lead acetate (P < 0.01). MDA content in blood and brain of animals treated with lead acetate 0.1% w/v, increased significantly (P <0.01), but these values were not significantly increased in other treated animals. No major histopathological alterations were detected in the brains of animals treated with lead acetate at 0.01% and 0.05% w/v. In animals treated with lead acetate 0.1% w/v, demyelinization and collagenous scar formation with neuronal atrophy in hippocampus region was observed. It is concluded that lead acetate induce oxidative stress which has an important role in brain damage in rats.

Effects of chronic lead acetate intoxication on blood indices of male adult rat

Abstract: Lead as one of the environmental pollutants can threats the life of living creatures in many ways. In this study, hematological effects of chronic toxicity of the lead acetate in adult male rats through measurement of the lead concentration in the blood of animal’s heart by atomic absorption as well as hematological analyses and differential cell count were investigated. Results showed that lead concentration in the treatment group was significantly higher than that of the control groups (P<0.001), and basophilic stippling, Howell-Jolly bodies, decreased RBC count (anemia), increased leukocyte count (leukocytosis), monocytosis, eosinopenia, neutrophilia, and thrombocytosis were observed in the test group (P<0.001). It is concluded that microcytic hypochromic anemia can be attributed to the interaction of lead with iron and copper metabolism and increased leukocyte count may be linked to the inflammatory effects of lead on lymphatic organs.

Combined efficacies of lipoic acid and meso-2,3-dimercaptosuccinic acid on lead-induced erythrocyte membrane lipid peroxidation and antioxidant status in rats

Abstract: One of the most intriguing phenomenon observed during lead toxicity has been attributed to lead-induced oxidative stress. The combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced alterations in selected parameters, which are indicators of oxidative stress in erythrocytes, have been studied. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce 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 week 6. Clinical evidence of toxic exposure was evident from the elevated blood lead levels (BPb) along with lowered levels of haemoglobin (Hb) and haematocrit (Ht). Lead-exposed animals showed enhanced membrane lipid peroxidation (LPO) in the erythrocytes. Damage to the erythrocyte membrane was evident from the decline in the activities of the transmembrane enzymes, viz., Na+, K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase. Lead-exposed rats also suffered an onslaught on the antioxidant defence system witnessed by lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH). Serum glutamic-oxoloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were also elevated in lead-exposed rats. Treatment with either LA or DMSA reversed the lead-induced biochemical disturbances encountered by the erythrocytes, but combined treatment with LA and DMSA was very effective in mitigating all the parameters indicative of oxidative stress.

Acute lead exposure induces renal haeme oxygenase-1 and decreases urinary Na+ excretion.

Abstract: The effects of acute lead exposure on renal function, lipid peroxidation and the expression of haeme oxygenase (HO) in rat kidney were determined. A single injection of lead acetate (50 mg Pb/kg) w...

Lead Reduces Messenger RNA and Protein Levels of Cytochrome P450 Aromatase and Estrogen Receptor β in Human Ovarian Granulosa Cells

Abstract: Exposure to lead causes decreased fertility in women. In the present study, we examined the in vitro effects of lead on cytochrome p450 aromatase (p450 arom) and on estrogen receptor beta (ERbeta), two key proteins for the human ovary. Aromatase is required for the bioconversion of androgen to estradiol; ERbeta mediates estrogen effects in granulosa cells. Granulosa cells were collected from women undergoing in vitro fertilization and then cultured with 10 microM lead acetate. Using atomic absorption spectrometry, we showed that lead accumulated in cells. Aromatase activity as measured by a tritiated water production assay was significantly reduced. Using semiquantitative reverse transcription-polymerase chain reaction and Western blotting procedures, we showed that p450 arom and ERbeta mRNA and protein content were both significantly reduced. Adding 10 microg/ml of cycloheximide, a protein inhibitor, did not eliminate the effects of lead. The present results support the hypothesis that the action of lead on fertility in women may result, in part, from the down-regulation of p450 arom and ERbeta gene transcription in ovarian granulosa.

Lead acetate genotoxicity on human melanoma cells in vitro

Abstract: In this study, chromosomal damage induced in vitro by lead acetate in human melanoma cells (B-Mel) was evaluated using the cytokinesis-blocked micronucleus assay and sister chromatid exchange (SCE) analysis. Lead acetate (10-6, 10-5 and 10-3 mM) induced micronuclei and SCE formation in a dose-dependent manner. Treated cells showed a decrease in cell viability but not concomitant cell death by apoptosis (lead acetate failed to induce internucleosomal DNA fragmentation at any of the doses tested). One important observation emerging from this study was that low-level lead exposure in vitro is able to induce significant cytogenetic damage in human melanoma cells, indicating an increased sensitivity of B-Mel cells to lead acetate.

The effect of lead ions on the energy metabolism of human erythrocytes in vitro.

Abstract: The aim of this work was to evaluate the influence of chronic exposure to lead ions on the parameters of energetic status of human erythrocytes in vitro. Umbilical cord erythrocytes were incubated with lead acetate at final lead ion concentrations ranging from 10 to 200 microg/dl. ATP, ADP, AMP, adenosine, GTP, GDP, GMP, guanosine, IMP, inosine, hypoxanthine, NAD and NADP concentrations in erythrocytes were determined using HPLC. Scanning electron micrographs of erythrocytes were taken. The mean concentrations of ATP, GTP, NAD and NADP, and mean values of adenylate energy charge (AEC) and GEC in cells incubated at the presence of lead ions were significantly lower after 20 h of incubation. Concentrations of purine degradation products (Ado, Guo, Ino) and Hyp were significantly higher. It is suggested that lead ions affect the energy metabolism of erythrocytes. Morphological changes in erythrocytes correspond to the increase of lead ions in the incubation mixture and to the decrease of ATP concentration in erythrocytes. A decrease in NAD and ATP concentration in erythrocytes could be a sensitive indicator of energy process disturbance, useful in monitoring in case of chronic lead exposure.

Developmental immunotoxicity of lead: impact on thymic function.

Abstract: BACKGROUND Since the potential effects of early exposure to lead on thymic functions have not been fully characterized, in this study we evaluated the capacity of lead to alter thymic function in juvenile chickens following embryonic exposure. METHODS Cornell K strain White Leghorn chicken eggs were administered lead acetate (400 μg/egg) or sodium acetate (control) on embryonic development (E12) with and without thymulin supplementation. Ex vivo production of interferon-γ (IFN-γ)-like cytokine by thymocytes and a delayed-type hypersensitivity (DTH) reaction were measured in the juvenile. Additionally, the effects of in vitro exposure to lead on both thymocytes and thymic stromal cells (TSCs) were evaluated. RESULTS Following E12 exposure to lead, ex vivo production of IFN-γ-like cytokine by juvenile-derived thymocytes decreased significantly compared to the control. The same effect was observed when thymocytes were directly exposed to lead in vitro and stimulated with thymic stromal supernatant. In contrast, when TSCs were exposed to lead in vitro, no change was seen in their functional capacity for promoting cytokine production. In ovo supplementation with thymulin partially reversed lead-induced DTH depression without any change in IFN-γ-like cytokine production. Embryonic exposure to thymulin alone partially depressed the DTH response. CONCLUSIONS These results suggest that lead can directly influence thymocyte function in the absence of the thymic microenvironment. Since thymulin levels may influence lead-induced immunotoxicity, embryonic endocrine status may be an important consideration. Lead exposure appears to alter thymic functions directly; however, indirect effects via endocrine factors are not precluded. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc.

Effect of lead acetate on the in vitro engulfment and killing capability of toad (Bufo arenarum) neutrophils.

Abstract: Lead is an element of risk for the environment and human health and has harmful effects that may exceed those of other inorganic toxicants. The immune system is one of the targets of lead. Its immunomodulatory actions depend on the level of exposure, and it has been demonstrated that environmental amounts of the metal alter immune function. Very little information is available regarding the effect of the metal on different aspects of the immune system of lower vertebrates, in particular of amphibians. The aim of this study was to investigate the effect of sublethal lead (as acetate) on the function of polymorphonuclear cells of Bufo arenarum. The results revealed that phagocytic and lytic functions of the adherent blood cells collected from sublethal lead-injected toads and incubated with suspensions of Candida pseudotropicalis were affected negatively. The decrease of the phagocytic activity was correlated with increased blood lead levels (P < 0.0001). Additional information referred to the total and differential leukocyte counts was presented; the only difference found was in the number of blast-like cells that resulted augmented in the samples of lead-injected toads. It was concluded that the evaluation of these parameters might be a reliable tool for the biological monitoring of the immune status of amphibians.

Morphine conditioned place preference is attenuated by perinatal lead exposure.

Abstract: The purpose of this investigation was to determine if perinatal lead exposure alters the conditioned reinforcing properties of morphine when offspring were tested as adults. Dams were gavaged daily with 0- (sodium acetate) or 16-mg lead (as lead acetate) for 30 days prior to breeding with nonexposed males. Administration continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). At PND 70 animals were tested in a conditioned place preference (CPP) preparation using 0.00, 0.60, 1.25, 2.50, or 5.00 mg/kg ip morphine as the unconditioned stimulus (US). Relative to controls, attenuation of CPP was evident in animals exposed to 16-mg lead at 1.25 and 2.50 mg/kg morphine. Analysis of blood lead concentration revealed that by the end of testing residue levels in metal-exposed animals had returned to control levels. However, data from littermates sacrificed well beyond the current testing period revealed that brain lead residues remained elevated in animals exposed to lead, even though the metal had gained clearance from blood. The present data suggest that early lead exposure may have an enduring impact on the reinforcing properties of morphine.

Serum vasoactive agents in lead-treated rats.

Abstract: Background: It is still unknown whether mechanisms of the hypertensinogenic effect of lead include changes in synthesis or release of vasoactive agents. This question is essential with regard to lead dissemination in the human environment as well as to frequent occurrence of arterial hypertension. Objectives: The aim of the study was to evaluate the effect of chronic exposure to lead on the vasoactive agents in blood in relation to redox system activity in vessel walls and to disturbances in homeostasis of essential metals. Using lead in double small, hypertensive doses we tried to estimate whether this effect dependents on the degree of lead exposure. Methods: The study was performed on the male Buffalo rats which were given lead in drinking water, 50 or 100 ppm (lead acetate dissolved in distillate water) for 12 weeks. Control rats were given distillate water. Rats were fasted starting the night before the experiment, and the next day were anesthetized intramuscularly with ketaminum at a dose of 300 mg/kg body weight. The abdomen was opened and the aorta was isolated. Blood samples were drawn from heart, abdominal and thoracic aorta and then kidneys were excised. Serum nitric oxide and prostaglandin PGF 2α concentrations were measured using RD 5% homogenates of aorta were prepared from thoracic fragment in saccharose buffer. Lipid peroxides in homogenates were determined colorimetrically and glutathione was measured using colorimetric assay BIOXYTECH GSH-400. The concentration of metals (lead, copper and zinc) in blood and aorta were determined with a plasma spectrometer. Results: The study shows different changes in toxicological and biochemical status, depending on the dose of metal. Mean serum nitric oxide concentration was higher in rats treated with lead in a dose of 50 ppm (p < 0.01) or 100 ppm (p < 0.001) than in the control group. The plasma endothelin-1 level was lower in rats given lead in a dose of 50 ppm (p < 0.05) than in controls, whereas serum prostaglandin PGF 2α concentration was similar in all animals. Glutathione concentration in aorta was higher in both groups of rats treated with lead (p < 0.001) in comparison to controls. There were positive linear dependencies between: (a) blood lead and serum nitric oxide; (b) aorta glutathione and serum nitric oxide; (c) copper in aorta and glutathione in aorta; (d) serum zinc and plasma endothelin-1 concentrations. Conclusions: It was concluded, that lead in small doses increases synthesis and/or releases nitric oxide and its concentration in serum. This effect of lead is probably connected with the augmented production of glutathione in vessel walls. Additionally, lead in a dose of 50 ppm provokes the decrease in the level of plasma endothelin-1, probably through the decreased level of serum zinc. We suppose that the mechanisms responsible for the vascular effect of lead differ even within the range of hypertensive doses.

The improvement of taurine in learning and memory ability of rats exposed to lead

Abstract: OBJECTIVE To investigate the improvement of taurine (Tau) in learning and memory ability of rats exposed to lead METHODS Forty Wistar rats were randomly divided into control group: treated with distilled water; lead group: treated with lead acetate (40 mgkg(-1)d(-1)); lead-taurine group 1, 2, 3: lead acetate (40 mgkg(-1)d(-1)) + different concentrations of taurine (100, 400, 800 mgkg(-1)d(-1)) The ability of learning and memory of rats were measured weekly by spatial water maze test from the 5th to 8th week At the end of the experiment, the rats were killed, the samples of blood and brain were taken for test RESULTS (1) The time of seeking anchorage of lead-Tau 800 mg group in the 6th, 7th, 8th week and that of lead-Tau 400 mg group in the 6th week were significantly lower than that of lead group (P<005) (2) Blood lead contents in lead-Tau 100 mg and lead-Tau 400 mg group [(5109 +/- 5756) microg/L, (48540 +/- 9885) microg/L] were different from those in lead group (P<005) (3) The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), nitric oxide synthase (NOS), acetylcholinesterase (AChE) in brain of lead-Tau 800 mg group and lead-Tau 400 mg group were also different from those in lead group (P<005 or P<001) The content of GSH and the activity of GSH-Px in lead-Tau 800 mg group were different from those in lead group (P<005) as well CONCLUSION Taurine could improve learning and memory ability of rats exposed to lead and may play a protective role in brain

Daily Rhythms in Blood and Milk Lead Toxicokinetics Following Intravenous Administration of Lead Acetate to Dairy Cows in Winter

Abstract: The objective was to investigate circadian variations of blood and milk lead toxicokinetics in dairy cows in winter Twenty lactating Holstein animals were randomly assigned to 4 treatments, corresponding to different hours after onset of light (HALO): 2, 8, 14 and 20 Cows received a single intravenous administration of 25 mg/kg lead as lead acetate Blood and milk samples were taken and analyzed by atomic absorption spectrophotometry For each toxicokinetic parameter, a one-way analysis of variance was performed to outline the existence of daily variations Significant differences as a function of HALO were detected in blood for the hybrid constant of elimination (β), half-life of elimination (t1/2β), area under the curve (AUC) and clearance (Cl) (p < 001) and volume of distribution at steady state (Vss) (p < 005) Half-life of elimination was highest when lead acetatae was injected at 2 HALO, and lowest following the 14 HALO administration Milk data showed significant differences for maximum con