Showing papers on "Lead acetate published in 1989"

Effects of lead acetate on cerebral glutathione peroxidase and catalase in the suckling rat.

Abstract: Exposure of immature rats to lead acetate results in hemorrhagic encephalopathy of variable evolution. As the maintenance of adequate protection against peroxides may be critical in this condition, the activities of selenium-glutathione peroxidase and catalase in cerebrum and cerebellum of suckling rats poisoned with lead acetate were studied from day six to day sixteen post-exposure. Age-related decreases of glutathione peroxidase and catalase activities in both controls and lead poisoned animals were observed. An increase in catalase activity was observed in cerebrum and cerebellum of lead-treated rats compared to controls. Glutathione peroxidase activity did not change significantly in cerebrum over the period studied. By contrast, glutathione peroxidase activity in cerebellum of lead-treated rats remained at about twice the control level over most of the study period. This apparent increase in glutathione peroxidase activity may be due either to a slower ontogenic decrease of its specific activity or to enzyme induction in response to oxidant stress in cerebellum.

Effects of lead on luteal function in rhesus monkeys.

Abstract: Exposure to lead in the workplace or home environment has been implicated as a cause of decreased fertility in women. In a previous study, as part of our effort to determine effects of lead in primates, female rhesus monkeys were exposed to lead acetate in drinking water (n = 10) or provided water with no added lead (n = 7) for 33 mo. Lead was administered at levels between 2 and 8 mg/kg/day, with doses adjusted to keep blood lead values near a target of 70 micrograms/dl (observed mean +/- SEM = 68.9 +/- 6.54 micrograms/dl). Blood lead concentrations in control animals were less than 10 micrograms/dl. No significant differences were detected between control and experimental animals in body weight, hematocrit, or general health. Female monkeys receiving lead exhibited longer and more variable menstrual cycles and shorter menstrual flow. In the present study, circulating amounts of progesterone (P4) were determined to evaluate luteal function during the final 7 mo of treatment with lead. Several characteristics were altered as a result of lead treatment: circulating amounts of P4 were reduced as indicated by relative units of area under the concentration-time curve, maximal amounts of P4 were reduced, and P4 levels were greater than 1 ng/ml on fewer days. There were no significant differences between groups in mean percent of anovulatory cycles. Therefore, although chronic treatment with the levels of lead used in this study did not prevent ovulation, luteal function was suppressed. These results extend previous observations of adverse effects of lead on ovarian activity and fertility in monkeys.

Dose-related Proximal Tubular Dysfunction in Male-rats Chronically Exposed To Lead

Abstract: Male Wistar rats were given 0.5 and 2% lead acetate in drinking water for 2 months, 1% lead acetate for 3 months and sodium acetate equimolar to 2% lead acetate for 3 months. Glucose, total proteins, lactate dehydrogenase (LDH), lysozyme and beta 2-microglobulin (beta 2-m) were measured in 24-h urine every month. Kidney weight and histology were also examined. At the three doses, lead exposure produced a significant elevation of the kidney weight. No significant change in urinary parameters was observed in rats given 0.5% lead acetate. Exposure to 1% lead acetate increased the urinary excretion of beta 2-m only. At the 2% lead acetate dose the elevation of beta 2-m excretion was accompanied by an increased urinary output of glucose, total proteins, lysozyme and LDH. Observations of the kidneys by light microscopy were in agreement with these biochemical findings. The nephrotoxic effect of acetate was excluded by the lack of biochemical or histological effects of sodium acetate on the kidney. It is concluded that a proximal tubular dysfunction is induced in rats chronically exposed to high doses of lead.

Combined nephrotoxicity of methylmercury, lead, and cadmium in Pekin ducks: metallothionein, metal interactions, and histopathology.

Abstract: This report describes the metallothionein (MT) levels and accumulation of mercury, lead, and cadmium, as well as their interaction with tissue zinc, copper, and iron, and the histopathological changes in kidneys of ducks exposed to methylmercury chloride (MeHgCl), lead acetate (PbAc), and cadmium chloride (CdCl2), singly or in combination for 13 wk. Forty-eight female Pekin ducks, divided into 8 groups of 6 birds each, were fed diets containing no added metals (control), 8 mg MeHgCl/kg feed, 80 mg PbAc/kg feed, 80 mg CdCl2/kg feed, 8 mg MeHgCl + 80 mg PbAc/kg feed, 8 mg MeHgCl + 80 mg CdCL2/kg feed, 80 mg PbAc + 80 mg CdCl2/kg feed, and 8 mg MeHgCl + 80 mg PbAc + 80 mg CdCL2/kg feed. Cadmium (Cd) when administered alone or in combination caused a 60-fold increase in kidney MT levels, while methylmercury (MeHg) or lead (Pb) administration caused a threefold increase in kidney MT levels. No significant changes in kidney MT levels were observed when metals were administered concurrently when compared with single-treatment groups. Residue analysis revealed accumulation of administered metals in kidney tissue. However, lead administration resulted in accumulation of small amounts of this element in kidney tissue. Simultaneous administration of MeHgCl and PbAc significantly increased the accumulation of lead in kidney when compared with PbAc-treated group. Cadmium when administered alone or in combination caused an increase in the levels of zinc and copper in kidney. Administration of MeHgCl or PbAc either alone or in combination caused increased iron levels in kidney, while cadmium administration either alone or in combination caused decreased iron levels. Administration of cadmium either alone or in combination caused degenerative changes in kidney proximal tubules. The severity of degenerative lesions increased when cadmium was simultaneously administered with other metals. These results indicate that combined administration of MeHg, Pb, and Cd has no significant effect on kidney MT levels or on essential elements in kidney tissue when compared with single metal groups. However, there appears to be an increase in the severity of histopathologic changes.

Ultrastructure of kidney of ducks exposed to methylmercury, lead and cadmium in combination.

Abstract: Ultrastructural alterations in the kidneys of Pekin ducks exposed to various combinations of methylmercury chloride (MeHgCl), lead acetate (PbAC) and cadmium chloride (CdCl2) for 12 weeks were studied. Eight groups (Gr), each consisting of 6 female ducks, were fed diets containing no heavy metals (control), 8 mg of methylmercury chloride (MeHgCl)/kg of feed (GrII), 80 mg of lead acetate (PbAC)/kg of feed (GrIII), 80 mg of cadmium chloride (CdCl2)/kg of feed (GrIV), 8 mg of MeHgCl + 80 mg of PbAC/kg of feed (GrV), 8 mg of MeHgCl + 80 mg of CdCl2/kg of feed (GrVI), 80 mg of PbAC + 80 mg of CdCl2/kg of feed (GrVII), and 8 mg of MeHgCl + 80 mg of PbAC + 80 mg of CdCl2/kg of feed (GrVIII). Renal corpuscles of the ducks treated with methylmercury (MdHg), lead (Pb), the cadmium (Cd), either alone or in two way combinations exhibited minor ultrastructural changes. The thickness of the glomerular basement membrane was significantly different from control only in Grs II, IV, V and VI. Crystallization of granules in the juxtaglomerular cells was also observed in Cd and Pb treated birds. Administration of the three metals in combination caused marked changes in podocytes withmore » fusion of secondary processes and no pedicle differentiation. The proximal tubule cells approximately (PT) accumulated lipid droplets, lysosomal bodies and membrane bound vacuoles in methylmercury treated birds. Lead exposed birds had a large number of secondary lysosomes and swollen mitochondria in PT cells. Cadmium administration caused degenerative changes in PT cells which included accumulation of lysosomal bodies containing degenerating organelles, lipid droplets and vacuoles containing myelin figures. Marked degenerative changes in PT cells and interstitial fibrosis was prominent when cadmium was concomitantly administered with the other metals.« less

Lead Inhibits Intracellular Killing of Leishmania Parasites and Extracellular Cytolysis of Target Cells by Macrophages Exposed to Macrophage Activating Factor

Abstract: Activation of Leishmanla enriettfl-lnfected mouse macrophages In vitro by treatment with macrophage activating factor (MAF)-rich media supplemented with Iipopoiysaccharlde (LPS) leads to rapid killing of the microorganism. When exposed to MAF + LPS in the presence of 30-100 �M lead acetate, however, macrophages failed to destroy the parasites. This effect was not due to lead toxicity for macrophages. Decreased microbicidal activity correlated with depressed respiratory burst as determined by measurements of glucose oxidation through the hexose monophosphate shunt (HMPS). Lead had little effect on Intracellular parasite killIng induced by exposure of macrophages to the electron carrier methylene blue; HMPS in such cells was similarly little affected, indicating that chemical triggering of this pathway bypassed the lead-imposed blockade. Lead also abolished macrophage activation measured by the lysis of tumor target cells in vitro. The metal failed, however, to Interfere with target-cell lysis by macrophages activated In lead-free medium, suggesting that lead inhibited the acquisition of the activated state rather than the functional expression of such state. Lead did not prevent the binding of radlolabeiled Interferon-y to macrophages; it did, however, slow down receptor turnover and degradation of bound interferon. Lead also inhibited the LPStrIggered cytotoxicity In macrophages previously exposed to interferon-’1’ in lead-free medium, suggesting that depressed intracellular killing might result from an effect on both the priming (interferon or MAF-dependent) and the triggering (LPS-dependent) steps of activation.

Interaction of L-ascorbic acid on the disposition of lead in rats.

Abstract: L-Ascorbic acid (As-Ac) has been investigated for its potential in the prophylaxis of lead poisoning. Using rats as the animal model, the pharmacokinetics of As-Ac was determined following a single intravenous dose (100 mg/kg) administered through a jugular vein. Plasma As-Ac levels were monitored using an enzyme assisted UV spectrophotometric method. The pharmacokinetic parameters of As-Ac obtained were used to establish a dosage regimen which could maintain its average plasma concentration of about 11 micrograms/ml at steady state in rats. The disposition of lead acetate (1 mg/kg) in rats was studied in the absence and presence of As-Ac at steady state. Lead concentrations were monitored in femur, kidney, liver and plasma over a 120 hr period using flameless atomic absorption spectrophotometry. In presence of As-Ac, femur, kidney and liver demonstrated 56, 22 and 41% respective reductions in their exposure towards lead. In addition, the half-life of lead in femur and plasma was found to be reduced by 27 and 51% respectively.

The statistical analysis of a carcinogen mixture experiment. III. Carcinogens with different target systems, aflatoxin B1, N-butyl-N-(4-hydroxybutyl)nitrosamine, lead acetate, and thiouracil.

Abstract: This paper describes factorial experiments designed to determine whether two carcinogens that lead to cancers in different organ systems act synergistically to produce cancers in Fischer 344 rats Four carcinogens, aflatoxin B1 (AFLA), N-butyl-n-(4-hydroxybutyl)nitrosamine (NBBN), lead acetate (LA), and thiouracil (THIO) were studied in pairwise combinations Each of the six possible pairs were studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses Methods of analysis designed explicitly for this study were derived to study interaction These methods were supplemented by standard statistical methods appropriate for single agent studies Neither synergism nor antagonism was demonstrated in these combined exposure studies Findings for male and female animals were consistent

Effects of Lead Salts on the Uptake, Release, and Binding of γ-Aminobutyric Acid: The Importance of Buffer Composition

Abstract: The effects of lead on the uptake and release of gamma-[3H]aminobutyric acid [( 3H]GABA) from rat brain slices were examined in solutions buffered with Tris-HCl, sodium phosphate, and sodium bicarbonate. Lead acetate (10-250 microM) inhibited uptake and potassium-stimulated release and facilitated spontaneous efflux only in solutions buffered with Tris-HCl. Calcium-independent binding of [3H]GABA was unaffected by lead acetate (1-100 microM) in Tris-citrate buffer but was significantly inhibited by 3 microM lead acetate in Tris-HCl solution. At the rat soleus neuromuscular junction, lead caused a dose-dependent reduction of end-plate potential amplitude at concentrations of 10-100 microM lead acetate in HEPES-buffered solution but had no effect at these concentrations in phosphate-buffered solution. Stability constants of lead complexes indicate that buffers containing carbonate and phosphate are unlikely to contain a significant concentration of Pb2+, as complexing by these anions would reduce the availability of free Pb2+. This study indicates that the choice of buffer is important when investigating the effects of lead on biological systems and that negative findings may result from the use of inappropriate buffers. It also has important clinical implications suggesting that some effects of lead poisoning may result from its ability to affect neurotransmitter systems directly and that local changes in pH and complexing anion concentrations in the CNS may influence its biological availability and, hence, variable biological responses.

Lead toxicity in chickens. Interaction with toxic dietary levels of selenium.

Abstract: Two experiments were conducted in which varying levels of lead (up to 2000 ppm as lead acetate trihydrate) and selenium (up to 40 ppm as Na2SeO3) were fed, either alone or in combination, to chicks from day-old through 18 or 20 d. Lead additions depressed growth in a dose-dependent manner without affecting mortality. Selenium addition at 20 ppm was severely growth inhibitory, but mortality was not affected. The growth inhibition of 20 ppm Se was partially alleviated by feeding it in combination with 2000 ppm Pb; however, mortality was increased significantly by the combination. In contrast 40 ppm Se resulted in almost complete cessation of growth and 85% mortality, whereas the combination with 2000 ppm Pb partially overcame the growth inhibition and eliminated the excess mortality. When Pb or Se were fed alone, hepatic levels of the fed element were elevated. There were further significant elevations of hepatic levels of both elements when fed in combination at identical dietary concentrations as the single element additions.

Neurotoxicity in rats sub-chronically exposed to low levels of lead.

Abstract: Pregnant rats (for prenatal exposure), 5-day-old rats, and 5-week-old rats were exposed orally to lead acetate daily for 10 weeks. Lead values in the brain of animals from all three lead-exposed groups were similar. Brain norepinephrine (NE) and GABA levels and glutamate decarboxylase (GAD) activity were decreased, and brain glutamate (glu), glutamine + asparagine (gln/asn), and tyrosine (tyr) levels, and monoamine oxidase (MAO) activities were increased in rats prenatally or 5 days postnatally exposed to lead. Brain ammonia, alanine (ala), aspartic acid (asp), and dopamine (DA) values were not affected by the prenatal or 5-day-postnatal lead treatment. Brain uptake index (BUI) values for glu were significantly elevated in rats exposed to lead prenatally or 5 days after birth. Exposure of 5-week-old rats to lead did not affect the brain catecholamine and amino acid levels. These results suggest that the brains of young rats were more sensitive to lead exposure than the brains of adult rats, although the accumulation of lead in brain was not affected by age.

Study of the inhibitory effect of lead acetate on duodenal contractility in rat

Abstract: SUMMARY 1 Abdominal colic and constipation are symptoms of lead poisoning in man, but mechanisms of these effects are not yet fully understood In this study the effect of lead acetate on contractility of rat duodenum was determined in vivo in 70 rats 2 Rats were orally dosed with 44 mg/kg per day lead as 53 mmol/L lead acetate, for 4 weeks Motility of the duodenum was recorded with an electrical impedance probe 3 A significant decrease in the amplitude of contraction waves in case of treated rats was observed compared with controls which received an equal volume of saline The number of contractions increased from 26 per min in controls to 33 per min in treated rats Gastrointestinal transit rate decreased by 64% and 69% after 9 and 15 days of lead exposure, respectively

Lead induced testicular changes in protein malnourished rats.

Abstract: The effect of concurrent low protein (8% casein) diet and lead (Pb) exposure (1 mg/ml lead acetate in drinking water) on testes of weaned rats up to 90 days of age was investigated Histopathological examination of testes of lead treated rats maintained on low protein diet revealed marked pathological changes associated with greatly reduced succinic dehydrogenase, glucose-6-phosphate dehydrogenase and adenosine triphosphatase activity as revealed histochemically compared to lead treated rats fed normal protein diet. It was concluded that higher accumulation of lead may be responsible for altering the enzyme levels and inducing the testicular degeneration to a greater extent in low protein fed rats compared to their counterpart controls.

Spermatogenesis and maturation of spermatozoa in rats exposed to lead

Abstract: The performed investigations have covered the effect of lead on the course of spermatogenesis, and on maturing and stored spermatozoa in epididymis. Moreover, the effect of this element, exerted on spermatozoa under in vitro conditions, has been evaluated. For intravital investigations the rats were given lead acetate during the period of 1 and 3 spermatogenesis, and throughout 1 seminiferous epithelium cycle. It has been disclosed that there was a delayed spermiation as well as release of immature spermatogenic cells in the tubules of testis. A transient weakening of 3 beta-HSD activity was seen to occur in the interstitial gland, whereas decreased concentration of testosterone was recorded in the blood. Changes observed in epididymis were decidedly more pronounced. A drop in the number of spermatozoa in the duct lumen as well as intensified phagocytosis of abnormal reproductive cells, and also reduced activity of SDH, particularly LDH, were revealed. The lead was found to handicap also the conduction in the autonomous nervous system of epididymis, which was evidenced by the absence of the duct wall tension and by the relaxed AChE and MAO activities. The spectrophotometric examinations have shown that the lead was accumulating to a considerable degree in epididymis, and in insignificant amount in the testis. The described changes within reproductive system kept increasing with the prolongation of the experiment. The detected minor changes in testis and markedly stronger in epididymis are likely to result from the direct, toxic action of the lead upon the epididymis. The in vitro examinations have demonstrated that spermatozoa live shorter in the presence of lead acetate, which supports the view that it exerts cytotoxic effect on the cells in question.

Lead inhibits oxidative metabolism of macrophages exposed to macrophage-activating factor.

Abstract: The present experiments were designed to evaluate the effect of lead on the capacity of macrophages to respond to activating signals by increased respiratory-burst activity. When mouse peritoneal macrophages were exposed for 24 h to macrophage-activating factor (MAF) and/or bacterial lipopolysaccharide in the presence of lead acetate, a marked inhibition of their oxidative metabolism was observed. The hexosemonophosphate-shunt (HMPS) activity and the release of oxygen derivatives upon triggering by phorbol myristate acetate (PMA) were impaired. Treatment with the metal for 1 h led, however, to stimulation rather than inhibition of the PMA-triggered superoxide production, suggesting that the metal interfered with neither the triggering steps nor the activity of the NADPH oxidase. Moreover, the lead-induced inhibition of macrophage oxidative metabolism did not result from blockade of enzymes of the HMPS pathway. Glucose-6-phosphate dehydrogenase in macrophage extracts, as well as CO2 production from glucose, remained unaffected by the presence of lead, and extracts of lead-treated macrophages were as active as extracts from control cells in those two assays. Lead appeared to interfere with an early event in the MAF-induced activation process. In addition, lead decreased the uptake of 2-deoxyglucose by macrophages, suggesting that the metal might inhibit trans-membrane glucose-transport systems, a phenomenon that might explain in part the metabolic inhibition observed in lead-treated cells.

Genotypic influences on lead-induced hyperactivity in mice

Abstract: Male mice, genetically selected for differences in brain weight or from a heterogeneous (HET) stock, were used to explore potential interactions between genotype and exposure to lead as manifested in activity. At the time of birth dams and their pups were given either water or a 0.5% lead acetate solution as the sole source of fluid. Fluid conditions remained constant throughout the experiment. The effects of chronic lead on activity in young adult mice depended on the genotype of the individual. Specifically, in an open field, HET mice exposed to lead tended to be more active than their control counterparts. Low-and high-brain weight lead-exposed mice at times were hypoactive but this effect depended on the specific nature of the measure.

Lead-dithiocarbamate interaction. Effect on ALAD activity in isolated rat hepatocytes.

Abstract: Dithiocarbamates are known to markedly increase tissue uptake of lead and potentiate toxic effects of lead in rats. Effects of the interaction between lead and diethyldithiocarbamate (DTC) on the enzyme δ-aminolevulinic acid dehydratase, ALAD, were studied in primary cultures of rat hepatocytes, incubated with lead acetate, PbAc, or lead-diethyldithiocarbamate complex, Pb(DTC)2, labeled with203Pb. Incubation of cells with the lipophilic Pb(DTC)2 complex caused a more rapid and stronger inhibition of ALAD activity than did PbAc. The effects on ALAD activity could be related to the cellular uptake of lead. Thus, a much higher and more rapid cellular uptake of lead was found following incubation with Pb(DTC)2 than with PbAc. Pb(DTC)2 inhibited ALAD activity also in vitro when incubated with purified ALAD enzyme. It is suggested that the increased inhibition of ALAD activity by Pb(DTC)2 is owing to facilitated cellular transport of lead in the complexed form and that complexing lead with DTC could serve as an experimental model in order to obtain high cellular concentrations of lead.