Showing papers on "Lead acetate published in 1981"
TL;DR: A compensatory mechanism operates to overcome the toxicity of ingested lead by maintaining a high concentration of glutathione in the liver and kidney in rat pups born of dams receiving a commercial laboratory diet supplemented with 0.5% lead acetate.
Abstract: The effect of lead poisoning on glutathione metabolism was studied in rat pups born of dams receiving a commercial laboratory diet supplemented with 0.5% lead acetate. Results showed that the body weight gain of the first 3 weeks of life and at the age of 6 weeks was significantly less in both male and female pups nourished by lead-fed dams than those raised by dams receiving the lab diet. Lead ingestion decreased hematocrit levels and hemoglobin values and increased the weights of liver, kidney, spleen and brain. Concentrations of plasma free histidine, glutamic acid and serine were decreased in lead-poisoned rats but glycine levels were markedly increased. After 4 weeks of lead feeding, both sexes had an increased glutathione concentration in erythrocytes, liver and kidney. Isotope studies further indicated that the incorporation of cystine-35S was significantly increased in glutathione but decreased in protein of liver and kidney of lead-fed rats. Similarly, lead ingestion significantly increased glycine-1-14C incorporation into renal glutathione. However, the activities of glutathione reductase and glutathione peroxidase were unaffected by lead poisoning. The data suggest a compensatory mechanism operates to overcome the toxicity of ingested lead by maintaining a high concentration of glutathione in the liver and kidney.
123 citations
TL;DR: It is demonstrated that hypertension induced by moderate levels of lead intake is associated with an increased vascular responsiveness to alpha-adrenergic agonists.
Abstract: The effects of lead on vascular responsiveness were examined in rats. Adult rats, which had received levels of lead acetate in their drinking water to produce blood levels similar to those seen in some urban human populations, consistently had higher systolic blood pressures compared to age-matched controls. Helical strips of tail arteries from the lead-treated rats displayed a greater force-generating ability in response to the cumulative addition of methoxamine to the muscle bath. There were no differences in ED50 between the two groups. Similar results were obtained when norepinephrine was used. The calcium-entry blocker, D 600, was less effective in reducing in reducing contractions induced by methoxamine in lead-treated rats than in controls. There were no differences between the two groups in responses to KCl or electrical stimulation of nerve endings. Contractile responses to norepinephrine, methoxamine, KCl, and nerve stimulation in arteries from untreated rats were unaltered by addition of lead acetate to the muscle bath. These results demonstrate that hypertension induced by moderate levels of lead intake is associated with an increased vascular responsiveness to alpha-adrenergic agonists.
74 citations
TL;DR: The increase in the amount of delta-aminolevulinic acid dehydratase in erythrocytes of lead-poisoned rats was suggested to be due to an increased rate of synthesis in the bone-marrow cells.
66 citations
TL;DR: Shortly after cessation of lead treatment, changes were observed in exposed animals in the development of motor activity, as well as in the disappearance of DA after synthesis inhibition, accumulation of labelled DA, and endogenous DA levels.
Abstract: Rats treated directly with water or lead acetate (25 or 75 mg/kg) on postnatal days 2 through 14 were tested for the development of spontaneous activity and for locomotor responses to d -amphetamine as weanlings. The development of striatal dopamine (DA) levels, uptake, release, and the disappearance of DA after synthesis inhibition were also examined. Blood and brain lead levels were markedly increased at 15 days in exposed animals; by 35 days blood lead levels had decreased 90% while lead level in neostriatum decreased only 55–60% The effects of the early lead exposure fell into two classes. Shortly after cessation of lead treatment, changes were observed in exposed animals in the development of motor activity, as well as in the disappearance of DA after synthesis inhibition, accumulation of labelled DA, and endogenous DA levels. As brain lead decreased from 15 to 35 days many of the behavioral and neurochemical abnormalities also dissipated. However, at 35 days, striatal DA levels remained decreased in animals given the higher lead dose with a resultant decrease in turnover rate and alterations were noted in activity responses to d -amphetamine in lead-treated animals.
60 citations
TL;DR: Blood lead concentrations were not a linear function of the oral dose in the rat, and the relationship between oral dose and toxic effects of lead may not be a simple one, so safe lead exposure levels in man are to be established via extrapolation of data from high levels of exposure.
53 citations
TL;DR: The overall analysis of the data indicated that the simultaneous exposure to manganese and lead, particularly with highest dose of the latter, may produce serious derangements in the behavioral pattern and levels of biogenic amines in the brain of rats.
Abstract: Groups of rats were exposed simultaneously to manganese chloride (3 mg Mn2+/ml water) through drinking water and lead acetate intraperitoneally at dosages of 5.0, 8.0 and 12.0 mg Pb2+/kg daily for a period of 14 days. The magnitude of changes in the behavioral pattern, contents of biogenic amines and accumulation of lead in the brain of rats simultaneously exposed to the two metals was significantly greater than observed in rats after exposure to either of the metals alone. A definite dose-response relationship was, however, noticed only with the changes in the motoractivity, norepinephrine, 5-hydroxytryptamine levels and in the accumulation of lead in rats simultaneously exposed to manganese and lead. The lowering in the contents of norepinephrine after combined treatment was found to be related with the decrease in the motoractivity in the rats. The exact role of depression in the levels of dopamine and 5-hydroxytryptamine in inducing marked impairment in learning ability and increased aggressive behavior in rats after the combined exposure to manganese and lead could not be ascertained. The overall analysis of the data indicated that the simultaneous exposure to manganese and lead, particularly with highest dose of the latter, may produce serious derangements in the behavioral pattern and levels of biogenic amines in the brain of rats.
50 citations
TL;DR: All the offspring that had been exposed to lead were less sensitive to the stimulus properties of d-amphetamine irrespective of whether or not they had continued on lead after weaning.
Abstract: Lead acetate (0.02 or 0.5 percent) was administered to dams throughout the lactation period with half of the litters continuing on lead after weaning. Drug thresholds for d-amphetamine were determined by using the drug-discrimination learning paradigm. All the offspring that had been exposed to lead were less sensitive to the stimulus properties of d-amphetamine irrespective of whether or not they had continued on lead after weaning.
47 citations
TL;DR: Data imply that, in spite of the similarities in the response of the lead and calcium absorptive processes to various treatments, there is no direct interaction between these cations in the intestine of the chick.
Abstract: The present study was designed to investigate, in more detail, the mechanism of lead transport by the gastrointestinal tract and particularly the similarities or dissimilarities between lead and calcium in this process. The absorption of these metals was determined in 3-week-old white Leghorn cockerels, raised on a commercial diet or special diets, using an in vivo ligated loop procedure. The dose administered into the loop usually contained 0.5 microCi 203Pb (and/or 0.1 microCi 47Ca), 0.01 mM lead acetate (and/or 1 mM CaCl2) in 0.5 ml of 0.15 M NaCl, pH 6.5. It was shown that lead is rapidly taken up by the intestinal tissue, and only slowly transferred into the circulation whereas calcium, also accumulated rapidly by the tissue, is rapidly released from the tissue in the serosal direction. The absorption processes of these cations show similar responses to various experimental conditions (low calcium intake, age of the animal, pH of the dosing solution). However, increasing luminal stable lead concentration from 0.01 to 1 mM Pb, significantly reduced the percentage of radiolead absorbed, but did not inhibit the absorption of radiocalcium, Also, luminal Ca (0-25 mM) did not significantly affect the absorption of 203Pb. These data imply that, in spite of the similarities in the response of the lead and calcium absorptive processes to various treatments, there is no direct interaction between these cations in the intestine of the chick.
46 citations
TL;DR: By the feeding of 0.82% lead on the intestinal responses to vitamin D and its metabolites was greatest in animals fed a low calcium or a low phosphorus diet, it was present with all diets tested.
Abstract: A study of the effect of ingestion of lead on the metabolism and function of vitamin D was carried out in rats fed diets varying in calcium and phosphorus content. The ingestion of 0.82% lead as lead acetate suppressed plasma levels of 1,25-dihydroxycholecalciferol in rats fed either a low phosphorus or a low calcium diet while it had no effect on this parameter in rats fet either a high calcium diet or a normal phosphorus diet. Most important, the ingestion of lead totally blocked the intestinal calcium transport response to cholecalciferol, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. On the other hand, the ingestion of lead acetate had no influence on the mobilization of calcium from bone, the elevation of serum inorganic phosphorus and in the mineralization of rachitic bone in the same animals. Thus by the feeding of 0.82% lead on the intestinal responses to vitamin D and its metabolites was greatest in animals fed a low calcium or a low phosphorus diet, it was present with all diets tested.
43 citations
TL;DR: The low level lead exposure effects manifested by immunosuppression indicate that immune dysfunction is a sensitive indicator of lead exposure.
41 citations
TL;DR: Lead levels in blood were highly correlated with the accumulation of lead in brain, femur, and kidney tissue in both groups of weanling rats, and in adult rats, significant correlations between blood lead and kidney lead and between blood and femur lead were found only in the rats receiving lead steadily in drinking water.
Abstract: The relative toxicity of low doses of lead acetate provided steadily in drinking water or by mouth once per week was studied in weanling and adult rats. Free erythrocyte protoporphyrin and urinary delta-aminolevulinic acid levels were measured, as well as lead levels in blood and kidney. The accumulation of lead in brain tissue and in bone (femur) was measured to determine the effect of age and schedule of administration on tissue distribution and retention of lead. Total intakes of lead during the 60-week experimental period were: weanling and adult rats exposed to drinking water supplemented with 200 microgram of lead acetate/ml: 127 +/- 10 mg and 160 +/- 16 mg, respectively; weanling and adult rats dosed with lead acetate orally once per week: 132 mg and 161 mg, respectively. Increased toxic effects of lead in the weanling animals were apparent in most of the parameters measured (urinary delta-aminolevulinic acid and blood, brain, femur and kidney lead levels). This pattern was observed in weanling rats exposed to lead steadily through drinking water or dosed orally with an equivalent quantity of lead once per week. Lead levels in blood were highly correlated with the accumulation of lead in brain, femur, and kidney tissue in both groups of weanling rats. In adult rats, significant correlations between blood lead and kidney lead and between blood lead and femur lead were found only in the rats receiving lead steadily in drinking water.
TL;DR: It is shown that milk consumption increases tissue-lead concentrations in rats fed low concentrations of lead and milk simultaneously, and Lactose appears to be the factor in milk responsible for this increase.
TL;DR: It was concluded from the study that calcium phytate might be employed as a natural protective factor against lead toxicity.
Abstract: Forty female MF1 mice were fed diets with and without calcium phytate. Addition of lead acetate resulted in toxic effects. After necropsy liver and kidneys were removed and analyzed for lead by flameless atomic absorption spectroscopy. Calcium phytate did not affect the nutritional status of the mice. It was concluded from the study that calcium phytate might be employed as a natural protective factor against lead toxicity. (JMT)
TL;DR: The results show that the resistance state of the mouse is impaired already by low doses of lead, and the leucocytosis that is normally induced in the animals by 1 μg endotoxin/kg b.w. was significantly reduced or completely suppressed.
Abstract: The half-life of the indian ink elimination (carbon clearance method) was used as a measure of the RES activity. A significant increase of the RES activity in mice was found already after a single intraperitoneal (i.p.) administration of 20, 50, or 100 μg PbAc/kg body weight (b.w.). A significant RES stimulation could also be demonstrated after a single or 10-day oral administration of lead at doses of 10–1,000 μg PbAc/kg b.w. No RES stimulation occurred, however, after 30-day oral administration of lead. On determining the reactivity of the RES to 1 μg endotoxin/kg b.w. it was found that it was already limited after a single and 10-day oral lead administration. After 30-day oral administration of lead (doses 10–1,000 μg PbAc/kg b.w.) the reactivity of the RES was completely suppressed. After a single and 10-day oral administration of lead (doses 10–1,000 μg PbAc/kg b.w.) we observed a marked leucocytosis. This effect was most clearly seen after a dose of 100 μg PbAc/kg b.w.; the leucocyte counts were increased by up to 50% in comparison with controls. After 30-day oral administration of lead, such a leucocytosis was no longer detectable. In accordance with the findings on the RES, the leucocytosis that is normally induced in the animals by 1 μg endotoxin/kg b.w. was significantly reduced or completely suppressed both after single and also after 10 and 30 days' oral administration of lead at doses of 100 and 1,000 μg PbAc/kg b.w. These results show that the resistance state of the mouse is impaired already by low doses of lead.
TL;DR: It is indicated that lead administration, eliciting blood levels of 450–550 μg/liter, produces a long-lasting selective electrophysiological deficit in developing brain in oculo.
TL;DR: The histologic structure of the testes was examined after treatment and group ‘Pb’ showed alteration of the histopathologic pattern and reduction in the size of seminiferous tubules, basal membrane separation and a decrease in the cell content of the germinal layer.
Abstract: Thirty-six healthy albino rats were divided into three groups and the histologic structure of the testes was examined after treatment: group ‘C’–10 healthy control rats were untreated; group ‘Pb’ – eight rats received intraperitoneal injections of 8.5 mg per kg body weight lead acetate for 154 days (15 doses in all); group ‘PbA’ – eight rats intoxicated with lead, like group ‘Pb’ but which, during the last 21 days before killing, were treated with 5 ml per kg body weight per day of a 2% injectable solution of sodium aspartate. As compared with the controls, group ‘Pb’ showed alteration of the histopathologic pattern and reduction in the size of seminiferous tubules, basal membrane separation and a decrease in the cell content of the germinal layer, lesions of the spermatocytes and spermatids, and slight oedematous dissociation in the interstice. In 75% of the group ‘PbA’ animals, normal aspects similar to those of group ‘C’ were found.
TL;DR: Administration of 0.13% lead acetate solution as drinking fluid to breeding mice was without significant effect on fertility, or weight of the offspring at age 1 day, and tissue lead concentrations were markedly raised by postnatal treatment.
TL;DR: It is demonstrated that lead's effects on activity are not invariant and the suggestion of an animal model for childhood hyperactivity is discussed.
Abstract: Mice were exposed to lead acetate (0.5%) pre- and postnatally, and activity levels were assessed at 21 days of age. Two measures of open field activity were employed at two different times of day across three doses of d-amphetamine. These factors influence the results observed in lead exposed mice and demonstrate that lead's effects on activity are not invariant. Implications for future research as well as the suggestion of an animal model for childhood hyperactivity are discussed.
TL;DR: Lead will decrease the hydroxylations of phenylalanine, tyrosine (the rate limiting step in catecholamine biosynthesis) and probably tryptophan and as a result, hyperphenylalaninaemia, deficiency of neurotransmitters and neurological dysfunction can be anticipated.
Abstract: Biosynthesis of 5,6,7,8‐tetrahydrobiopterin is significantly inhibited in vitro by 10‐7M lead acetate whilst salvage by dihydropteridine reductase is irreversibly inhibited by 10‐6M lead acetate. Therefore lead will decrease the hydroxylations of phenylalanine, tyrosine (the rate limiting step in catecholamine biosynthesis) and probably tryptophan. As a result, hyperphenylalaninaemia, deficiency of neurotransmitters and neurological dysfunction can be anticipated.
Journal Article•
TL;DR: The results suggest that the lead exposure levels used were at or near a no-effect level for several common neuro behavioral tasks and that kidney weight may be a more discriminative index of excess lead exposure than some simple neurobehavioral indices.
Abstract: Motor impairments and seizures are frequent neurologic sequelae of excess lead exposure in children. To evaluate the relative significance of such symptoms in an animal model, Long-Evans rats were lead-exposed from parturition to weaning by adulteration of the dams' drinking water with 0.02% or 0.2% lead acetate. Ontogeny of swimming ability from 6 through 24 days of age was not altered by postnatal lead exposure. Rotorod performance was tested on 21, 30, 60, 90, 150 and 440 days of age and was maximal in rats 30 through 150 days of age, with the poorest performance by 440-day-old rats. Rotorod performance was decreased by both levels of lead exposure and this effect was most evident at 60 and 150 days of age. Both levels of lead exposure increased kidney weights of dams at weaning and the 0.2% lead acetate exposure decreased hematocrit of dams. Kidney weights of lead-exposed pups were not increased at 10 days of age, but pups in the 0.2% lead acetate group had increased kidney weights at 20, 90 and 150 days of age. Hematocrit values of pups in the 0.2%, but not in the 0.02%, lead acetate exposure group were decreased at 20 days of age. No effects of lead exposure on hematocrits were found at 10, 90 or 150 days of age. Wet weight of brain, cerebellum, adrenals, spleen and thymus were not altered at any age by postnatal lead treatment. In a second study, Sprague-Dawley rats exposed to lead via dams drinking 0.2% lead acetate throughout gestation and lactation. Pre- and postnatal lead exposure did not alter the ontogeny of electro-shock seizure thresholds in rats tested on 8 through 20 days of age. The results suggest that the lead exposure levels used were at or near a no-effect level for several common neurobehavioral tasks and that kidney weight may be a more discriminative index of excess lead exposure than some simple neurobehavioral indices.
TL;DR: Treatment-related renal changes were found in the proximal tubules; they consisted of a dose-related increase in the amount of lysosomes in epithelial cells of the convoluted part, and of severely damaged cells and loss of brush border in the straight part.
Abstract: Electron microscopical studies were carried out on the kidneys of rabbits given s.c. injections of 0 (control), 0.25 or 0.50 mg lead acetate/kg b.w. 3 times a week during 14 weeks. At the end of the experimental period the animals had lead blood levels of 60, 500 and 600 micrograms/l whole blood respectively. Treatment-related renal changes were found in the proximal tubules; they consisted of a dose-related increase in the amount of lysosomes in epithelial cells of the convoluted part, and of severely damaged cells and loss of brush border in the straight part. There was also an increase in lysosomal tubular inclusions, which are considered characteristic of lysosomes of the proximal tubular cells of the rabbit kidney. The significance of these findings for assessing the risk of occupational exposure to lead is briefly discussed.
TL;DR: A comparison of lead concentrations between the organs of rats dosed days 1–10 and rats dose days 11–20 indicated that the latter accumulated less lead per gram of tissue (p < 0.05) than their younger litter mates.
Abstract: Newborn rat pups were treated in seven groups: Group 1, the control, was untreated and killed at birth (day 1); Groups 2, 3, and 4 were treated on postnatal days 1 through 10 with respectively saline or lead acetate, 5.0 mg/kg and 7.5 mg/kg body weight; Groups 5, 6, and 7 were treated with the same respective dosages on days 11 through 20. Cerebellum, cerebral cortex, brainstem plus hippocampus, liver, and blood were analyzed for lead. Neonatal rats killed at birth all contained some lead, the cerebellum having the highest concentration. Tissue from most treated groups accumulated lead in a dose-dependent manner. A comparison of lead concentrations between the organs of rats dosed days 1–10 and rats dosed days 11–20 indicated that the latter accumulated less lead per gram of tissue (p < 0.05) than their younger litter mates.
TL;DR: It was concluded that pharmacological challenges on activity may be sensitive indicators of lead exposure, but the type of activity measure is critical.
Abstract: In Experiment 1, rats were given a 1% lead acetate diet from Day 100 of life to the termination of the experiment. After 82 days of lead feeding behavioral tests were started. Lead exposure increased wheel-turning hyperactivity produced by food deprivation and phenylethylamine injection. Lead produced no activity change in the unchallenged condition. In the open field, lead-exposed rats were less responsive to the stimulating action of PEA and amphetamine and to the sedating action of pentobarbital. In Experiment 2, the interaction of lead with food deprivation or PEA on wheel-turning was replicated in naive animals given only a 32-day exposure. Chemical analysis was made of tissues. Ingested lead entered the brain. Regional steady-state levels of brain norepinephrine, dopamine and serotonin were not altered by lead treatment when measured following four days of starvation at a time when lead-induced behavioral change was distinct. It was concluded that pharmacological challenges on activity may be sensitive indicators of lead exposure, but the type of activity measure is critical.
TL;DR: The incorporation of [3H]thymidine into liver DNA of rats stimulated by the injection of DMN was strikingly suppressed by the injections of cupric acetate (20 mg Cu/kg), but that of rats stimulating by thejection of DEN was not suppressed byThe suppressive effect of copper.
Abstract: The incorporation of (3H)thymidine into liver DNA of rats increased 6--8 times 48 h after a single injection of dimethylnitrosamine (DMN, 30 mg/kg) and diethylnitrosamine (DEN, 100 mg/kg). To test the suppressive effect of copper, the incorporation of (3H)thymidine into liver DNA in the DMN groups or DEN groups pretreated with copper was measured 48 h after the administration of DMN or DEN. The incorporation of (3H)thymidine into liver DNA of rats stimulated by the injection of DMN was strikingly suppressed by the injection of cupric acetate (20 mg Cu/kg), but that of rats stimulated by the injection of DEN was not suppressed by the injection of copper. Some other metal salts, silver nitrate (20 mg Ag/kg), nickel acetate (20 mg Ni/kg) and basic lead acetate (20 mg Pb/kg) did not significantly suppress the incorporation of (3H)thymidine stimulated by DMN or DEN. The accumulation of copper was much higher in the liver of copper-administered rats than that of nickel or lead in the liver of nickel-administered rats or lead-administered rats. The accumulation of silver was comparatively high in the liver of silver-administered rats.
TL;DR: Erythrocyte factors are concerned in the inhibition of delta-aminolaevulinic acid dehydratase (ALA-D) by lead at 20 to 100 nM concentrations, and Reinhibition of lead worker enzyme with normal Hb fraction may be deleted not only by heating but also by zinc or DTT as well.
Abstract: Erythrocyte factors are concerned in the inhibition of delta-aminolaevulinic acid dehydratase (ALA-D) by lead at 20 to 100 nM concentrations. The activity of the factors in detected in Hb fractions from Sephadex G-200 gel filtration of erythrocyte supernatant. After gel filtration of erythrocyte supernatant from a lead worker, 50% of lead is found in ALA-D fractions, although the fractions recover from ALA-D inhibition. The recovered activity is reinhibited if the enzyme fraction is preincubated with Hb fraction obtained from the same chromatography. Similarly obtained enzyme from a normal subject is also inhibited when it is preincubated with normal Hb fraction and lead acetate at 20 to 100 nM concentrations. The extent of the inhibition depends on the concentrations of Hb fraction and lead acetate preincubated. Reinhibition of lead worker enzyme with normal Hb fraction may be deleted not only by heating but also by zinc or DTT as well. Hb fraction heated at 60 degrees C for 5 min is also able to induce the lead-inhibition of the activity in ALA-D fraction. Half life of the factors is 26 min at 60 degrees C and 3 min at 80 degrees C.
TL;DR: Oral lead intake in adult rats bearing intraocular brain grafts yields blood and brain levels which are physiologically relevant to problems of clinical lead toxicity, taken together with previous reports on animal and human lead exposure.
TL;DR: The histological, histochemical, and electron-microscopic findings support the biochemical data about certain disturbances in the energy supply and utilization in the liver tissue.
Abstract: Liver changes after separate and combined action of vibration (whole body, 100 Hz, 0.1 mm amplitude) and other factors: noise (white noise 105 dB/A), heat (35°C, humidity 45–55% and air velocity 0.2–0.3 ms−) and lead (lead acetate, 20 mg/kg) were studied in white rats. The exposure lasted for 2 h daily during 10 days (lead was daily applied per os in a water solution). After the treatment in liver homogenates the activity of SucDH, LDH, and ATP-ase, as well as the quantity of soluble proteins (SP) and -SH gr were determined. In fresh frozen liver slices the activity of SucDH, LDH, and ATP-ase were investigated. Liver samples were studied by light and electromicroscopy. The results show that vibration alone did not produce marked changes, but when the other factors acted simultaneously, more expressed alterations in the liver were found. The most pronounced changes were obtained after vibration and lead effect. The histological, histochemical, and electron-microscopic findings support the biochemical data about certain disturbances in the energy supply and utilization in the liver tissue.
TL;DR: Ringed turtle doves receiving lead treatment had excessive lead concentration in their kidneys and cell necrosis was apparent, and lead intranuclear inclusion bodies were identified in the proximal convoluted tubule cells.
TL;DR: Although these data showed lower bioavailability of lead in oyster meat as compared with lead acetate, the intercept of the lines at 25 ppm dietary lead suggests that the relative bioavailability may be reversed at lower levels of lead intake.
TL;DR: The hepatic sequestration of lead provides a basis for altered hepatic function and consequent sensitization to endotoxin by suppressing hepatic localization of the heavy metal by preventing lead-potentiated endotoxic shock and associated hepatic dysfunction.