Influences of thiamin on lead intoxication, lead deposition in tissues and lead hematological responses of Tilapia zillii.

1. Lead levels in the blood, kidney, liver, brain and muscle of fish receiving only lead were elevated markedly over the values of both controls and thiamin-treated fish. 2. No statistical difference was observed between the lead levels in bone samples of both fish receiving only lead and thiamin-treated fish. 3. In contrast to the fish receiving only lead the fish treated with thiamin appeared to be healthy and had no lead poisoning signs. 4. Over the period of study, hemoglobin content and red blood cell counts of fish receiving only lead showed significant decreases from the values of both controls and fish treated with thiamin. 5. Hematocrit values and white blood cell counts were uninfluenced by either lead exposure or thiamin treatment at all intervals. 6. The data suggest that thiamin can serve as a promising natural chelator to prevent fish mortality, not only in short term, but also in prolonged exposure.     

Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius)

One-day old American kestrel (Falco sparverius) nestlings were orally dosed daily with 5 microliters/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.     

Plasma and erythrocyte lipid peroxide levels in workers with occupational exposure to lead

The plasma and erythrocyte lipid peroxide levels were measured in a group of male subjects occupationally exposed to lead for an average period of 17 yr, and compared to those from an age-matched control group living in the same city in a similar socioeconomical environment. The blood lead and plasma zinc levels were measured by atomic absorption spectroscopy. The plasma and erythrocyte lipid peroxide levels were established by the malondialdehyde determination method. Significant differences were found in the blood lead levels in lead-exposed workers, 15.00±10.15 μg/dL as compared to controls, 2.37±0.89 μg/dL. The plasma (2.67±0.69 μM) and erythrocyte (27.53±6.28 nmol/g Hb) lipid peroxide levels in workers with occupational exposure to lead were significantly higher than controls, 1.23±0.61 μM and 14.35±2.08 nmol/g Hb, respectively. There were no significant differences of the zinc levels in both groups. The blood lead levels had a statistically significant positive correlation with age and with duration of exposure in both groups, but showed no relationship to the corresponding blood zinc levels. The results presented in this study indicate that the increase of plasma and erythrocyte lipid peroxide levels in workers exposed to lead may be related to the lead concentration, age and duration of exposure.     

Changes in selected haematological parameters in juvenile chinook salmon subjected to a bacterial challenge and a toxicant

An infection and a toxicant were presented singly and in combination to juvenile chinook salmon. The fish were challenged with Renibacterium salmoniarum and exposed to two levels (0.05 and 0.50 × 96 h LC50) of the toxicant sodium pentachlorophenate. The experiment comprised measurement of seven blood parameters and observations on mortality and behaviour at 4-day intervals over a period of 40 days.
All fish receiving the combined treatment of bacterial challenge and higher level of toxicant died 12 days post-infection on the 8th day of toxicant exposure. Mortalities also occurred in the groups of diseased fish and fish receiving the toxicant alone. There were no mortalities in the appropriate control groups of unchallenged fish in clean water.
Most of the haematological changes pointed to a general haemodilution probably arising from progressive damage to the kidney and haematopoietic tissue by bacteria but which did not appear to be greatly affected by combined exposure to the toxicant. The blood parameters of the fish in clean water as well as those exposed to just the toxicant remained relatively constant. Higher mortality and sustained lower values of haematocrit, haemoglobin and glucose concentrations as well as red blood cell counts were present in both the diseased group of fish held in clean water and the disease plus low level toxicant group compared to the control fish; white blood cell counts were low initially but increased markedly as the infection progressed. This latter treatment combination also produced lower total protein and blood urea nitrogen concentrations.     

Effects of lead shot ingestion on selected cells of the mallard immune system

The immunologic effects of lead were measured in game-farm mallards (Anas platyrhynchos) that ingested lead shot while foraging naturally, mallards intubated with lead shot, and unexposed controls. Circulating white blood cells (WBC) declined significantly in male mallards exposed to lead by either natural ingestion or intubation, but not females. Spleen plaque-forming cell (SPFC) counts were significantly lower in mallards intubated with lead pellets compared to controls. Declines in WBC and SPFC means with increasing tissue lead concentrations provide further evidence that lead exposure reduced immunologic cell numbers. Hormonal activity and diet may have influenced the immunologic effects of lead exposure in this study.     

Decreased thiamine and magnesium levels in the potentiation of the neurotoxicity of lead in occupational lead exposure

The relationship between blood lead (Pb) and serum levels of calcium and of neural nutrients such as thiamine and magnesium (Mg) has been determined in a Nigerian population that is occupationally exposed to Pb. Forty-seven male Pb workers were recruited as test subjects and 25 males unexposed to Pb served as controls. The test subjects were classified into three groups, based on severity of exposure to Pb. Blood lead (BPb) and the serum levels of Mg, thiamine, and calcium were determined in both test subjects and controls. The mean blood Pb level was not significantly higher in Pb workers. In contrast, Mg and thiamine levels were significantly decreased (p<0.05; p<0.01, respectively). However, the calcium level was not significantly lower in test subjects than in controls. Also, there was a significant negative correlation between serum thiamine and blood Pb levels (r=-0.50; p<0.01). Furthermore, there was a significant negative correlation between serum calcium and BPb levels (r=-0.41; p<0.01). This study has shown that relatively low BPb levels can enhance Pb absorption and also potentiate Pb neurotoxicity in the presence of decreased serum thiamine and Mg levels.     

Blood pressure relationship to nitric oxide, lipid peroxidation, renal function, and renal blood flow in rats exposed to low lead levels

The results of experiments designed to show that inhibition of nitric oxide production in rats exposed to low lead levels increases vascular resistance, decreases renal blood flow and glomerular function, and enhances oxidative stress. Forty-five adult male Sprague-Dawley rats were divided into four groups. Group A was used as controls and consisted of rats that received no treatment; group B acted as NO-inhibited controls by receiving L-NAME (N(G)-nitro-l-arginine methyl ester) as the NO inhibitor; group C was injected intraperitoneally with 8 mg/kg lead acetate for 2 wk; and group D receiving lead acetate plus L-NAME. Compared to healthy controls, significant elevation of the mean (p<0.01), systolic (p<0.04), and diastolic (p<0.01) blood pressures was found in the lead-treated rats. The renal blood flow was 1550+/-468 blood per unit (bpu) in the controls, 488+/-220 bpu in the L-NAME controls, 1050+/-458 bpu in the lead-treated group, and 878+/-487 bpu in the Pb plus L-NAME group. Low-level lead exposure did not change the urinary flow rate, creatinine clearance, and the creatinine, potassium, phosphorus, glucose, and protein excretion in 24-h urine. In the lead plus NO-inhibited rats, a significant decrease in sodium ion excretion was observed (p<0.01). The NO levels of the lead exposed, L-NAME-treated controls, and L-NAME plus lead-exposed groups are significantly lower compared to untreated controls: p<0.002, p<0.001, and p<0.01, respectively. When compared to untreated controls, the plasma malondialdehyde levels were not significantly different in the lead exposed, lead plus L-NAME, and L-NAME control groups. These results suggest that lead-induced hypertension might be related to a decrease of NO and consequent vasoconstriction, rather than to a decrease of renal blood flow or to decreases in renal sodium.     

S-adenosyl-L-methionine a counter to lead intoxication?

The effect of S-adenosyl-L-methionine (SAM) administration to both acute and chronic lead exposed mice was investigated. SAM was given s.c. at different doses and for different time intervals. The best results were obtained using 20 mg SAM/kg applied daily over a period of 20-22 days. Results obtained in both acute and chronic lead poisoning were quite similar. GSH concentration in blood and liver, reduced in intoxicated animals was increased after SAM administration reaching normal values. Blood, liver and kidney lead content notably increased at the beginning of SAM treatment and decreased rapidly in the group receiving SAM, attaining values near control levels in 2 weeks. A significant recovery of blood, liver, kidney, spleen and brain delta-aminolevulic acid dehydratase (ALA-D) initially reduced in poisoned animals, was clearly produced after SAM administration. A clear and direct correlation between the recovery of both ALA-D activity and GSH levels and the decreased concentration of lead in tissues was observed, reinforcing our proposal that enhancement of thiol content as a result of SAM administration would facilitate the detoxification process and lead removal, consequently reversing the inactivation of the enzyme. We conclude that SAM therapy is beneficial in the treatment of lead intoxication.     

Chelation therapy in workers with lead exposure.

Occupational lead overexposure remains a major problem. To evaluate the settings in which physicians appropriately prescribe chelation therapy for lead exposure, 7 cases were identified from physician phone calls and mandatory laboratory reporting of elevated blood lead levels to the California Department of Health Services. In the 2 workers with the highest blood lead levels (both of whom had severe symptoms), treatment was indicated. Physicians inappropriately prescribed chelating agents to workers with ongoing lead exposure as prophylaxis against rising blood lead levels and to treat atherosclerotic heart disease. Workers'' personal physicians identified lead overexposure in 5 of the 7 cases. Workplace lead medical surveillance programs mandated by the federal Occupational Safety and Health Administration were inadequate in all 5 of the workplaces where information was available.     

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin–renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4 mg/100 g, subsequent doses 0.05 mg/100 g, im) or vehicle for 30 days. Treatment increased lead blood levels (12 μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1 nM–100 mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on R_max decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A₂/prostaglandin H2 receptor antagonist SQ 29,548, TXA₂ synthase inhibitor furegrelate, EP₁ receptor antagonist SC 19220, and ACE inhibitor and AT₁ receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O₂⁻ liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT₁ receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb²⁺ (12 µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin–angiotensin system activity.     

Seasonal variations in the level of immunoglobulins and serum proteins of children differing by exposure to air-borne lead

A semicohort of children, initial age about 11.5 years, from an exposure area near a secondary lead smelting plant (E group children) was examined for some humoral immune response parameters in the blood and saliva and compared to a group of control children matched by age living in a relatively unpolluted rural area (Co group children). All examinations were performed every autumn and spring over a period of 2 successive years, and the data included in the final analysis were only from children who had completed at least 3 of the 4 examination series performed. To sum up, children from area E showed a clearcut elevation of mean blood lead (Pb) levels with marked seasonal fluctuations peaking in spring; Pb levels in the blood of Co group children had no such season-related fluctuation patterns and tended to slightly decline over the two years of observation. Delta-aminolevulinic acid dehydratases (ALAD) levels in area E were of distinctly lower mean values than in area Co, but no correlation with mean blood Pb levels could be observed. Levels of IgG were more or less inversely correlative with Pb levels in both sexes, levels of IgM showed a distinct downward trend in E group children at all samplings. Total serum protein (SP) levels of children from area E showed a reverse correlation with plumbemia, secretory IgA (sIgA) concentrations showed a decrease in E group children of both sexes, but the values tended to converge with control values. Levels of alpha 1-antitrypsin (A 1-AT) showed marked season-related fluctuation patterns in Co children, the curves in E group children turned steeply upward from the third examination series on. Ceruloplasmin (CPL) levels in E group children had a clearcut upward trend at three subsequent blood samplings, the curves in Co group children continued to drop. Children from area E showed markedly higher frequency rates of abnormal values than did children from Co area.     

Effects of lead and hyperthermia on prenatal brain growth of guinea pigs

The effects of lead at blood levels of 100 micrograms/100ml or less on the brains of young animals have not been clearly defined, and little is known of its effects and interactions with other agents on prenatal brain development. This study examined the effects of subclinical doses of lead acetate given to pregnant guinea pigs on the development of the embryo brain. At 9 A.M. on day 20 or 21 of pregnancy, guinea pigs were given 6, 12.5, or 25 mg/kg body weight of 0.5% lead acetate in distilled water by intraperitoneal injection. Some of the animals at each dose rate were also exposed to hyperthermia at 11 A.M. on the day of injection and the following day. Another group was exposed to hyperthermia without lead treatment. A saline-treated control group was used for comparison. Mean levels of lead in blood 1 hour after dosing ranged between 65 and 128 micrograms/100 ml and at 24 and 72 hours between 65 and 96 micrograms/100 ml. Brain weights of newborn guinea pigs in the 12.5- and 25-mg lead acetate group were significantly reduced compared with control values. Body weights of all groups receiving lead were not significantly different from those of controls. There was no indication of interaction between hyperthermia and lead acetate in doses of 6 or 12.5 mg/kg. At 25 mg/kg plus hyperthermia, there appeared to be a strong synergistic response, with an incidence of 88% micrencephaly compared with 5% in the group given 25 mg/kg without hyperthermia and 46% in the hyperthermia without lead group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biomonitoring of a population of Portuguese workers exposed to lead

Lead is a heavy metal that has been used for many centuries and it is still used for various industrial purposes thanks to its physical and chemical characteristics. Human exposure to lead can result in a wide range of biological effects depending upon the level and duration of exposure. Despite the fact that lead has been found capable of eliciting genotoxic responses in a wide range of tests, not all studies have been conclusive. Although several experimental studies have shown that lead may modulate immune responses, data in exposed humans are still preliminary. The purpose of our study was to evaluate the genotoxic and immunotoxic effects of lead exposure in a group of 70 male workers from two Portuguese factories. The control group comprised 38 healthy males. The exposed individuals showed significantly higher levels of lead in blood and zinc protoporphyrin, and significantly lower δ-aminolevulinic acid dehydratase activity than the controls, suggesting a relatively high lead exposure. Nevertheless, the limit of 70 μg/dl for lead in blood established by the Portuguese regulation was never reached. Results of the comet assay were not modified by the exposure, but a significant increase in the mutation frequency in the exposed workers was obtained in the T-cell receptor mutation assay. Furthermore, data obtained in the analysis of the different lymphocyte subsets showed a significant decrease in %CD8+ cells and a significant increase in the %CD4+/%CD8+ ratio in exposed individuals with regard to the controls. No clear effect was observed for vitamin D receptor genetic polymorphism on the parameters evaluated. In view of our results showing mutagenic and immunotoxic effects related to lead exposure in occupational settings, it seems that the Portuguese biological exposure limit for lead needs to be revised in order to increase the safety of exposed workers.     

Low level environmental lead exposure--a continuing challenge

The current threshold for lead toxicity, defined as a blood lead level of 10 mug/dL, was adopted by the United States (US) Centers for Disease Control and Prevention (CDC) in 1991 and the World Health Organization in 1995. Since that time, adverse health outcomes at blood lead levels below this threshold have been well demonstrated. Most concern probably relates to children of pre-school age; an international pooled analysis has demonstrated lead-associated intellectual deficits at blood lead levels well below 10 mug/dL. In the case of adults, several convincing population studies have shown a positive association between blood lead and risk of death. The largest such study compared mortality information from participants with blood lead levels in the highest third of the blood lead distribution (3.6 mug/dL or greater) with those in the lowest third (less than 1.9 mug/dL). After adjustment for potential confounders, estimates of the excess risk were 25% for all cause mortality and 55% for cardiovascular mortality. The adverse consequences of lead exposure have no discernible blood lead threshold, implying there is no safety margin at existing exposure levels. Despite marked declines in population mean blood lead levels since 1980, low level environmental lead exposure remains a significant public health concern.     

Hemograms for and nutritional condition of migrant bald eagles tested for exposure to lead

Plasma proteins, hematocrit, differential blood counts were examined and nutritional condition was estimated for bald eagles (Haliaeetus leucocephalus) trapped (n = 66) during antumn migration, 1994-95 at Galloway Bay (Saskatchewan, Canada), for the purposes of estimating prevalence of exposure to lead. Sex and age differences in hematocrit and plasma proteins were not observed; however, female eagles exhibited larger median absolute heterophil counts than males. Hematologic values were similar to those previously reported from eagles in captivity. Departures from expected hematological values from a healthy population of eagles were not observed in birds with elevated levels of blood lead (> or =0.200 microg/ml). Similarly, nutritional condition was not related to blood-lead concentrations. Therefore, it appears that lead exposure in this population was below a threshold required to indicate toxicological alteration in the hematological values and index of nutritional condition that we measured.     

Genotoxic effects of occupational exposure to lead and cadmium

This study was designed to assess genotoxic damage in somatic cells of workers in a Polish battery plant after high-level occupational exposure to lead (Pb) and cadmium (Cd), by use of the following techniques: the micronucleus (MN) assay, combined with in situ fluorescence hybridization (FISH) with pan-centromeric probes, analysis of sister chromatid exchanges (SCEs), and the comet assay. Blood samples from 44 workers exposed to lead, 22 exposed to cadmium, and 52 unexposed persons were used for SCE and MN analysis with 5'-bromodeoxyuridine (BrdU) or cytokinesis block, respectively. In parallel, the comet assay was performed with blood samples from the same persons for detection of DNA damage, including single-strand breaks (SSB) and alkali-labile sites (ALS). In workers exposed mostly to lead, blood Pb concentrations ranged from 282 to 655 microg/l, while the range in the controls was from 17 to 180 microg/l. Cd concentration in lead-exposed workers fell in the same range as for the controls. In workers exposed mainly to cadmium, blood Cd levels varied from 5.4 to 30.8 microg/l, with respective values for controls within the range of 0.2-5.7 microg/l. Pb concentrations were similar as for the controls. The incidence of MN in peripheral lymphocytes from workers exposed to Pb and Cd was over twice as high as in the controls (P<0.01). Using a combination of conventional scoring of MN and FISH with pan-centromeric probes, we assessed that this increase may have been due to clastogenic as well as aneugenic effects. In Cd- and Pb-exposed workers, the frequency of SCEs as well as the incidence of leukocytes with DNA fragmentation in lymphocytes were slightly, but significantly increased ( P<0.05) as compared with controls. After a 3h incubation of the cells to allow for DNA repair, a clear decrease was found in the level of DNA damage in the controls as well as in the exposed workers. No significant influence of smoking on genotoxic damage could be detected in metal-exposed cohorts. Our findings indicate that lead and cadmium induce clastogenic as well as aneugenic effects in peripheral lymphocytes, indicating a potential health risk for working populations with significant exposures to these heavy metals.     

Influence of L-lysine and zinc administration during exposure to lead or lead and ethanol in rats

Influence of lysine and zinc administration on the lead-sensitive biochemical parameters and the accumulation of lead during exposure to lead or lead and ethanol was investigated in rats. The lead exposure inhibited blood δ-aminolevulinic acid dehydratase (ALAD) activity, increased blood zinc protoporphyrin (ZPP), urinary δ-aminolevulinic acid (ALA), serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), blood and tissue lead levels, and decreased blood and hepatic glutahione (GSH) contents. Some of these effects were enhanced on coexposure to ethanol. The simultaneous administration of lysine and zinc reduced tissue accumulation of lead and most of the lead-induced biochemical alterations irrespective of exposure to lead alone or lead and ethanol. The depletion of endogenous calcium and magnesium owing to lead or ethanol exposure was also prevented by co-administration of lysine and zinc.     

Kinetic parameters of the inhibition of red blood cell aminolevulinic acid dehydratase by triethyl lead and its reversal by dithiothreitol and zinc

In chronic or acute exposure to triethyl lead, a de novo synthesis of aminolevulinic acid dehydratase (δ-ALAD) in bone marrow and an increased activity in circulating red blood cells can be demonstrated by activating the enzyme with dithiothreitol (DTT) and zinc. We determined the median inhibitory concentration and the apparent inhibition constant for triethyl lead on δ-ALAD. After dosing with triethyl lead, in vivo inhibition of ALAD only occurred at the high dose, but activation analysis in vitro showed increased ALAD activity to be present at all dose levels in a dose-dependent fashion. The use of an activation assay for red blood cell ALAD may have value as a bio-effects monitor of exposure to organic lead.     

Different sensitivity of carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) to the immunomodulatory effects of UVB irradiation

In order to study the sensitivity of two fish species, carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss), to the immunomodulatory effects of ultraviolet B (UVB) radiation, the fish were exposed to a single UVB dose of 50, 250, 500 or 1,000 mJ cm(-2). These species represent different phylogenetic groups of fish, and they differ also in their behaviour inhabitating often dark and turbid (carp) or clear and transparent waters (salmonids). Immune responses were studied on day 1 post-irradiation. Unexposed fish, and fish exposed to radiation depleted of UV wavelengths served as controls. UVB irradiation markedly enhanced the blood respiratory burst and cytotoxic activity in carp, but in the head kidney these parameters were significantly suppressed. Rainbow trout respiratory burst was affected only after exposure with the highest dose of UVB. Lymphopenia and granulophilia were noted in both fish blood after exposure. This study indicates that UVB irradiation modulates immune functions in both fish species studied, and that rainbow trout is more tolerant than carp against UVB. Fish are clearly adapted to the environmental UVB levels prevailing in their usual living habitats, but are also a target of undesired effects of UVB on immune functions whenever exposed to increased radiation levels.     

Impact of the California lead ammunition ban on reducing lead exposure in golden eagles and turkey vultures

Predatory and scavenging birds may be exposed to high levels of lead when they ingest shot or bullet fragments embedded in the tissues of animals injured or killed with lead ammunition. Lead poisoning was a contributing factor in the decline of the endangered California condor population in the 1980s, and remains one of the primary factors threatening species recovery. In response to this threat, a ban on the use of lead ammunition for most hunting activities in the range of the condor in California was implemented in 2008. Monitoring of lead exposure in predatory and scavenging birds is essential for assessing the effectiveness of the lead ammunition ban in reducing lead exposure in these species. In this study, we assessed the effectiveness of the regulation in decreasing blood lead concentration in two avian sentinels, golden eagles and turkey vultures, within the condor range in California. We compared blood lead concentration in golden eagles and turkey vultures prior to the lead ammunition ban and one year following implementation of the ban. Lead exposure in both golden eagles and turkey vultures declined significantly post-ban. Our findings provide evidence that hunter compliance with lead ammunition regulations was sufficient to reduce lead exposure in predatory and scavenging birds at our study sites.