Hematological changes in rats chronically exposed to oral aluminum

This study was aimed to investigate the effects of the long-term oral exposure to aluminum sulfate on hematological parameters in rats. For this purpose, 24 adult female Wistar rats were divided in three groups with 8 animals each (control, citrate, and citrate plus aluminum groups). Rats from control and citrate groups had free access to tap water and to a sodium citrate solution (35 mM), respectively. Rats from citrate plus aluminum group received, as unique source of liquid, an aluminum sulfate solution (30 mM) diluted in the above-mentioned sodium citrate solution, ad libitum. After the treatment period (18 months), aluminum-exposed rats showed a significant decrease in the number of red blood cells, blood hemoglobin concentration and hematocrit when compared to rats from the control group. Serum iron levels were also significantly lower in citrate plus aluminum group, whereas total iron binding capacity did not change after citrate plus aluminum exposure. Erythrocyte thiobarbituric acid-reactive substances (TBARS) and nonprotein thiols (NPSH) levels, erythrocyte osmotic fragility and hepatic delta-aminolevulinic acid dehydratase (delta-ALA-D) activity did not change after treatment with citrate plus aluminum. Conversely, aluminum exposure increased delta-ALA-D activity in bone marrow. The present results indicate that long-term oral exposure to low doses of aluminum sulfate promotes alterations on erythrocyte parameters in rats, probably as a consequence of alterations in the iron status. In addition, although the details of the underlying mechanism remain unclear, our study reports, for the first time, a stimulatory effect of chronic aluminum exposure on bone marrow delta-ALA-D activity.     

Relationship between activation of delta-aminolevulinic acid dehydratase by heating and blood lead level

Both blood lead and erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity were determined for workers with and without an occupational lead exposure.In workers occupationally exposed to lead, it was demonstrated that the erythrocyte ALA-D is markedly activated by heating the hemolysate at 60° C for 5 min and there is a good positive correlation between the ratio of heated to nonheated ALA-D activity and the blood lead level (r = 0.799). In addition, by heating the hemolysate, the ALA-D activity of the lead-exposed workers appears to be returned into the normal range regardless of the extent of lead absorption. However, in normal workers without the occupational lead exposure, no significant correlation was found between the ratio of heated to nonheated ALA-D activity and the blood lead level, although the normal ALA-D also can be slightly activated by heating the hemolysate at 60° C for 5 min.     

In vivo regulation of delta-aminolevulinate dehydratase activity

The interrelationships among purified delta-aminolevulinate dehydratase (ALA-D; EC 4.2.1.24) activity, Pb, and ALA-D concentrations were studied in vitro. The ratio of Pb to the ALA-D subunit, but not the Pb concentration, determined the relative activity of ALA-D, indicating the significance of the amount of ALA-D in studying the mechanism of enzyme inhibition by Pb. To elucidate the in vivo mechanisms of ALA-D regulation, male Wistar rats, 6 months old, were treated with Pb, Zn, and glutathione (GSH) separately or in combination for 130 days. After Pb administration, the amount of ALA-D, as determined by radioimmunoassay, increased in the presence and in the absence of the Zn-GSH pretreatment, even if the enzyme activity were higher (the Zn-GSH-Pb-treated rats) than that of the control. Zn and GSH restored the enzyme activity in vivo synergistically. Since immunochemical study showed the identity of the liver ALA-D with the erythroid ALA-D, the liver and erythroid data were pooled to quantify the interrelationship among ALA-D activity, and Pb, Zn, SH, and the enzyme concentrations. The equation was the relative activity of ALA-D (%) = 0.256.[Pb/ALA-D subunit]2 - 9.56.[Pb/ALA-D subunit] - 0.000281.[square root Zn.SH/ALA-D subunit]2 + 0.0898..[square root Zn.SH/ALA-D subunit] + 33.6 (multiple correlation coefficient = 0.909, n = 108, p less than 0.01). The result indicated that 83% of the in vivo regulation of ALA-D activity is explained when the four factors, Pb, Zn, SH, and ALA-D concentrations, are considered in combination.     

Relationship between lead concentration in blood and the activities of erythrocyte pyrimidine 5′-nucleotidase and delta-aminolevulinate dehydratase in the mice exposed to lead

The relationship between the activities of both pyrimidine 5-nucleotidase (Py5N) and delta-aminolevulinate dehydratase (ALA-D) in erythrocytes and the concentration of lead in blood was investigated in the mice which were given ad libitum a drinking water containing lead of 10 to 500 ppm, for 30 days.From these results, it was demonstrated that the erythrocyte PySN activity is inhibited by lead and its activity level is negatively correlated with the concentration of lead in blood (r=–0.78). In addition, it was suggested that the erythrocyte Py5N activity is a better indicator in the exposure to relatively high lead concentration while the ALA-D is a more sensitive indicator for evaluating the lead exposure of low and moderate levels.     

Chemical and biological monitoring of chronic lead poisoning in the rat. Implications to the assessment of hazard of low-level lead

A study on rats of the effects of lead on delta-aminolevulinate dehydratase (ALA-D) activity, and its pH-dependent maximal enzyme activity is reported. Over a 5-week period, the lead burden and ALA-D activity in kidney, liver and brain are documented. Lead concentrations in the organs, expressed as micrograms/g protein are in the sequence kidney greater than liver greater than brain and reach essentially a constant level after 3 days of exposure. This is consistent with the existence of an efficient mechanism removing lead from these organs. Lead affects the ALA-D in all three organs by reducing the activity and shifting the pH of maximum enzyme activity to more acidic values. In common with the lead levels, the ALA-D activity does not deteriorate beyond the levels reached after 3 days of exposure. The existence of a mechanism removing lead from the organs is further supported in a recovery study on blood and kidney, in which both lead level and ALA-D activity return essentially to normal values after 7 days of no exposure to lead.     

Effect of Zinc or S-Adenosyl-l-methionine on Long Term Administration of Low Doses of Lead to Rats

Two alternatives for the treatment of lead intoxication, administration of zinc or a thiol donor, S-adenosyl-L-methionine (SAM), were analysed. Rats were exposed to lead (Pb)-acetate (60 mg/1) in drinking water during 90 days; one group also received SO₄Zn in water (40 mg/l), while another received both Pb and SAM (5 mg/24 hr intraperitoneally. Erythrocytic δ-aminolaevulinic dehydratase (ALA-D) activity was significantly reduced (P<0.001) both in rats receiving Pb alone and in rats receiving Pb and each of the other two treatments. The high erythrocytic uroporphyrinogen synthetase (URO-S) activity noticed in Pb administered rats, was significantly (P< 0.001) reduced in animals treated either with zinc or with SAM. Hepatic ALA-D activity tended to decrease while renal enzyme activity was not modified by the low level Pb exposure used in this work. Interestingly, SAM treated rats in both tissues exhibited significantly (P<0.01) higher activities of the enzyme. It is argued that SAM treatment causes a surplus of thiols that allows the full expression of ALA-D catalytic activity.     

Comparative study of effects of lead on the activity of erythrocyte pyrimidine 5′-nucleotidase and delta-aminolevulinate dehydratase in vivo and in vitro

The effect of lead on the activities of erythrocyte pyrimidine 5′-nucleotidase (Py5N) and delta-aminolevulinate dehydratase (ALA-D) was studied in the mice which were given ad libitum a drinking water containing lead of 10, 50 and 250 ppm, for 27 days. The erythrocyte Py5N activity was not decreased in all groups of lead-exposed mice. However, the erythrocyte ALA-D activity was markedly decreased in the groups exposed to 50 and 250 ppm lead. These data indicate that erythrocyte ALA-D is more sensitive than Py5N to lead in vivo. On the other hand, from the in vitro study, it was demonstrated that the human erythrocyte Py5N is moderately inhibited by zinc and tin, and markedly by mercury, cadmium, silver, copper, and lead, at 10⁻⁴ molar concentrations. In addition, it was observed that the erythrocyte Py5N is most remarkably inhibited by mercury while the ALA-D by lead, among metals tested.     

Arsenite-enhanced procoagulant activity through phosphatidylserine exposure in platelets

Numerous epidemiological studies have reported the close relationship between arsenic in drinking water and cardiovascular disease (CVD), yet the exact mechanism underlying this relationship remains unclear. We investigated whether arsenic can affect the procoagulant activity of platelets, which are essential in blood clotting, thrombus formation, and progression of CVD. While arsenite alone did not induce procoagulant activity, it significantly enhanced thrombin-induced procoagulant activity of human platelets in a concentration- and time-dependent manner. In flow cytometric analysis, arsenite potentiated phosphatidylserine (PS) exposure and microparticle (MP) formation, the major mediators of procoagulant activity. Arsenite-enhanced calcium increase and subsequent calpain activation were found to be involved in these effects, as determined by confocal microscopy and gel electrophoresis. Arsenite also inhibited flippase, an enzyme that restores PS to the inner leaflet, suggesting that PS could be retained in outer membranes after exposure. Consistent with these in vitro results, ex vivo studies revealed that PS exposure in platelets was significantly increased after acute or chronic arsenic exposure in rats. Most notably, in a rodent in vivo venous thrombosis model, arsenite indeed led to increased thrombus formation. In conclusion, arsenite-enhanced procoagulant activity in platelets by PS exposure and MP generation ultimately results in accelerated thrombus formation in vivo, suggesting that this enhanced activity is a possible contributing factor in CVD associated with chronic exposure to arsenic through drinking water.     

Effects of gentamicin sulfate on enzyme activities of carbonic anhydrase from human erythrocytes in vitro and from rat erythrocytes in vivo

The effects of gentamicin sulfate on carbonic anhydrase (CA) enzyme activity in in vitro human and in in vivo rat erythrocytes were investigated. For in vitro study, human carbonic anhydrase-I and -II (HCA-I and HCA-II) were purified by affinity-column chromatography, and rats were used for in vivo study. In vivo and in vitro CA enzyme activity was determined colorimetrically using the CO2-hydration method of Wilbur and Anderson as modified by Rickli et al. Gentamicin sulfate (1.98-9.90 mM) showed in vitro inhibitory effects on HCA-I and HCA-II hydratase activity up to a 2 mM concentration, when determined using the C02-hydratase method. Rat erythrocyte CA activity was significantly inhibited for up to 3 h (p<0.001) following intramuscular administration of gentamicin sulfate to Sprague-Dawley rats (3.2 mg/kg body weight). In conclusion, gentamicin sulfate inhibits CA enzyme activity in vivo and at low concentrations in vitro, but activated it at high concentrations (> or = 4 mM) in vitro.     

Environmental lead exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in maternal and cord blood.

The hypothesis that environmental lead exposure measured from blood (Pb-B) inhibits delta-aminolevulinic acid dehydratase activity (ALA-D) from whole blood was tested in 241 urban mothers and their newborns. Geometric means and (5th and 95th Percentiles) for maternal and cord Pb-B were 6.4 microg dl(-1) (3.4-11.9) and 4.6 microg dl(-1) (2.8-9.2). Spearman correlations between mother and cord Pb-B and ALA-D were all negative but statistically significant only for cord Pb-B and mother ALA-D. A potential lead threshold, was identified between 3.2 and 4.8 microg dl(-1), above which ALA-D may be inhibited by lead, and below which ALA-D may be insensitive or even activated. In conclusion, low environmental exposure to lead is responsible for a demonstrable biochemical effect. This potential ALA-D inhibition may lead to neurotoxic effects, especially in newborns who have high level of neurogenesis.     

Decreased erythrocyte delta-aminolevulinate dehydratase activity after styrene exposure

delta-Aminolevulinate dehydratase (ALA-D:porphobilinogen synthase, 5-aminolevulinate hydro-lyase, EC 4.2.1.24) activity was depressed markedly in red cells of rats exposed to 0.21 g/m3 styrene, a chemical widely used in commercial products. The depression was not restored in vitro after treatment with dithiothreitol and zinc. Consistent with this finding, radioimmunoassay of the enzyme protein demonstrated reduction in the enzyme concentration by styrene exposure. There was a good correlation between the decrease in enzyme activity and its concentration in the styrene-treated animals, suggesting that the depression of the enzyme activity was essentially due to the reduction in the enzyme content. Decrease in the enzyme content in bone marrow cells to almost the same extent as that in erythrocytes seems to indicate the decreased synthesis of ALA-D in the bone marrow. In vitro studies showed that styrene 7,8-oxide, the major intermediate of styrene metabolism, decreased the activity of purified ALA-D but that styrene, the parent compound itself, had no inhibitory effect. The activity and concentration of erythrocyte ALA-D in workers chronically exposed to styrene were also depressed significantly. These findings indicate that the styrene exposure-mediated decrease of ALA-D activity in erythrocytes was a reflection of reduction in the enzyme protein, which may have been the result of styrene 7,8-oxide action, and they suggest that a similar process may also be involved in the reduction of erythrocyte ALA-D in styrene-exposed workers.     

Effect of treatment with mercury chloride and lead acetate during the second stage of rapid postnatal brain growth on δ-aminolevulinic acid dehydratase (ALA-D) activity in brain, liver, kidney and blood of suckling rats

The sensitivity of developing rodents to toxic metals differs considerably from that of adults. In the present study, we investigated the in vivo and in vitro effects of inorganic mercury and lead on δ-aminolevulinic acid dehydratase (ALA-D) from brain, liver, kidney and blood of young rats. Eight day-old rats were injected with one or five doses of lead acetate (0, 3.5, or 7.0 mg/kg) or HgCl₂ (0, 2.5, or 5.0 mg/kg). In vitro, the IC₅₀ for mercury inhibition of cerebral, renal and hepatic ALA-D was in the 124 to 160 μM range, while values for lead acetate was in the 7 to 12 μM range. The IC₅₀ of blood enzyme for lead (0.8 μM) and mercury (6.5 μM) was significantly lower than that observed for the other tissues. A single dose of lead did not affect the enzyme activity, but a single dose of HgCl₂ (5 mg/kg) caused a significant inhibition of ALA-D from kidney (40%, P < 0.01) and liver (25%, P < 0.05). Five doses of lead acetate (3.5 or 7 mg/kg) caused an inhibition of about 25 and 40%, respectively (P < 0.01), of hepatic ALA-D, and an increase of 1.4-fold (P < 0.05) and 2.6-fold (P < 0.01) of blood enzyme, respectively. Treatment with five doses of HgCl₂ (5 mg/kg) caused an inhibition of about 25, 60, 50, and 80% of ALA-D from brain, blood, liver and kidney, respectively (all P < 0.05). Five doses of 2.5 mg/kg HgCl₂ caused an inhibition of ALA-D from liver (40%, P < 0.01) and kidney (45%, P < 0.01). These results demonstrate that ALA-D from young rat tissues show different sensitivities to mercury and lead. The enzyme was more affected by mercury than by lead in vivo, while in vitro lead was more potent that mercury as an ALA-D inhibitor.     

Bioavailability of Aluminum from Drinking Water

Bioavailability of Aluminum from Drinking Water. FULTON, B.,JAW, S., AND JEFFERY, E. H. (1989). Fundam Appl. Toxicol. 12,144–150. Aluminum, present in our drinking water as hydroxideor sulfate, is limited by solubility to 2.5 mg/liter at pH 7.0.This study was carried out to determine if aluminum at dosestypically found in drinking water would accumulate in rat tissuesif a ligand such as citrate at neutral or acid pH is coadministered,or in the absence of citrate at acid pH. Al(OH)₃ or AlCl₃ wasgiven ad libitum in drinking water to male Sprague-Dawley ratsat 0, 0.1, 2.0, or 100 mg/liter, in 4 mM acetate, pH 3.2 (A),4 mM citrate, pH 2.6 (C), 4 mM citrate, pH 7.0 (7C), or distilledwater, pH 7.0(W). After 10 weeks, rats were killed and tissueswere wet-ashed in nitric acid for determination of aluminumby flameless atomic absorption. Copper, iron, and zinc weredetermined by flame atomic absorption. Metal ion concentrationsin tibia, brain, liver, blood, and kidney did not differ significantlybetween treatment groups. Aluminum accumulated in intestinalcells of all 100 mg Al/liter rats, with the C group accumulatingmore aluminum than the A or W groups. In the C group, intestinalaluminum content increased significantly in a dose-dependentmanner. Intestinal iron was decreased significantly in all the100 mg Al/liter groups. Intestinal copper was decreased in theW group at 100 mg Al/liter, with a trend toward a decrease inA and C groups. We conclude that at these low levels studied,aluminum accumulates in intestinal tissue, and that this accumulationis enhanced by citrate ligand. At 100 mg Al/liter, intestinaliron accumulation is decreased, and copper accumulation is marginallydecreased.     

Physiological disturbances in rainbow trout, Salmo gairdneri (R.), exposed at two temperatures to effluents from a titanium dioxide industry

Rainbow trout (Salmo gairdneri R.) were exposed to the supernatant waste water (260 μl/l) from a TiO₂ producing plant in a continuous flow test (Diluent: brackish water 7‰) for 2 wk at two temperatures (7–8 and 13–15°C). Presedimentation chambers were used to separate the solid, precipitated fraction of the waste water from the soluble part.After 2 wk of exposure the fish were killed and blood samples for hematological and biochemical analyses were taken via caudal vessels. The effect pattern of the fish exposed at low temperature (7–8°C) differed from that of the fish exposed at 13–15°C. The exposure at 13–15°C significantly increased the blood hematocrit level and increased the plasma sodium and chloride concentrations. Moreover, increased plasma glucose and lactate contents were found in these fish. These parameters were unaffected in the fish exposed at 7–8°C. Instead this group suffered from a plasma hypocalcemia and a sex-dependent inhibition of erythrocytic delta-aminolevulinic dehydrates (ALA-D) enzyme activity.The effects obtained at 13–15°C were characterized as general stress symptoms. However, the effects obtained at 7–8°C indicated a more serious toxic response of the exposed fish. The reason behind this more pronounced effect at low temperature is assumed to be related to a higher concentration of metals present in the waste water at low temperature.     

Phenobarbital enhances the aldehyde dehydrogenase activity of rat hepatocytes in vitro and in vivo

Aldehyde dehydrogenase (ALDH) was measured in primary cultures of hepatocytes obtained with collagenase perfusion from livers of Long-Evans rats. After seven days in culture, basal ALDH activity, protein content and DNA content are significantly decreased. Exposure of the cultures to phenobarbital (PB, 3 mM in the media) does not prevent the decrease of DNA content, although it keeps protein at relatively higher levels. The activity of ALDH is not only preserved, but also significantly enhanced, when propionaldehyde, phenylacetaldehyde, benzaldehyde and D-glucuronolactone are used as substrates and NAD as the coenzyme. A relative increase of activity is also noted when ALDH is measured with benzaldehyde and NADP. Treatment of Long-Evans animals with PB (1 mg/ml, in drinking water for 2 weeks) leads to similar relative increases of the ALDH activity. In absolute values, however, enzyme activities found after in vivo treatment with PB are higher, compared to those obtained after in vitro exposure. These results show that ALDH activity can be greatly enhanced by PB in primary hepatocyte cultures, free from any indirect endogenous influences.     

Rates of spontaneous reactivation and aging of acetylcholinesterase in human erythrocytes after inhibition by organophosphorus pesticides

The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (R1R2) and diethoxy substituted (R1R2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology. A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure.     

Amiodarone is a pharmacologically safe drug for porphyrias

Amiodarone (AD) is an effective antidysrythmic drug, however, there can be serious side effects, such as hepatic and neurological alterations, as well as skin photosensitization, as seen in porphyrias. Clinical signs in porphyrias might be triggered by the so-called porphyrinogenic drugs. Without sound basis, Amiodarone has been classified as an unsafe drug for porphyric patients. The aim of this work has been to study the effect of AD, both in vivo and in vitro, on heme metabolism. In the in vivo assays, the activities of 5-aminolevulinate synthetase (ALA-S), ALA dehydratase (ALA-D), porphobilinogenase (PBGase) and PBG-deaminase (PBG-D) in blood, liver, and kidney; hepatic and fecal porphyrins, urinary ALA, PBG and porphyrins in male mice strain CF1 treated with AD (100 mg i.p. daily) for 1 week and 1 month, were measured. No significanat differences were found for any of these parameters in the AD treated animals as compared to controls. In the in vitro experiments human blood, and mice blood, liver, and kidney, were used to measure the activities of ALA-S, ALA-D, PBGase, PBG-D and uroporphyrinogen decarboxylase, in the presence of varying concentrations of AD (0.0172-4.304 mM). AD did not modify any of the enzyme activities. All of the above biochemical parameters were studied in 17 cardiac patients under AD treatment for 3 to 20 years. Neither the activities of the heme enzymes, nor the levels of precursors and porphyrins in urine and plasma were altered. These findings clearly demonstrate that AD is a pharmacologically safe drug and can be used for the treatment of associated pathologies in porphyrias.     

Lead-induced procoagulant activation of erythrocytes through phosphatidylserine exposure may lead to thrombotic diseases

Lead (Pb) is a ubiquitous heavy metal pollutant in various environmental media, especially in food and drinking water. In human blood, about 95% of lead is associated with erythrocytes, suggesting that erythrocytes could be an important target of lead toxicity in the cardiovascular system. Recent studies suggested that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure and resultant procoagulant activation. We investigated the effects of lead on the procoagulant activity of erythrocytes using in vitro human erythrocyte and in vivo rat models. In a flow cytometric analysis, lead (Pb2+) enhanced PS exposure on human erythrocytes in a concentration- and time-dependent manner. The concentration of lead (1-5 microM) used in the current investigation is well within the ranges observed in blood from lead-exposed populations. PS exposure by lead appeared to be mediated by increased intracellular calcium levels as shown by 19F-NMR and intracellular ATP depletion. Consistent with these findings, the activity of scramblase, which is important in the induction of PS exposure, was enhanced, whereas the activity of flippase, which translocates exposed PS to inner membrane, was inhibited by lead treatment. Furthermore, lead-exposed erythrocytes increased thrombin generation as determined by a prothrombinase assay and accelerated the coagulation process initiated by tissue factor in plasma. These procoagulant activations by lead were also confirmed in vivo. Administration of lead significantly enhanced PS exposure on erythrocytes and, more importantly, elevated thrombus formation in a rat venous thrombosis model. These results suggest that lead exposure can provoke procoagulant activity in erythrocytes by PS exposure, contributing to enhanced clot formation. These data will provide new insights into the mechanism of lead-induced cardiovascular diseases.     

In vivo effects of lead on erythrocytes following chronic exposure through drinking water

More than 95% of lead, a environmental heavy metal, entering into blood accumulates in erythrocytes suggesting erythrocytes as an important target of lead toxicity. Recent studies reported that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However, in vivo effects of chronic lead exposure especially by drinking water on procoagulant activity of erythrocytes have not been studied yet. In the present study, we investigated the effects of chronic exposure of lead by drinking water on erythrocytes in rats. Groups of 40 male rats were provided with drinking water containing various concentrations of lead for 4 weeks and complete blood cell count, procoagulant activities of erythrocytes and platelets were evaluated with basic inspections on body weight and food/ water consumption. The administration of lead containing drinking water increased the blood lead level (BLL) in a dose-dependent manner up to 22.39 +/- 2.26 microg/dL. Water consumption was significantly decreased while food consumption or body weight gain was not affected. In contrast to the "previous findings with acute lead exposure, chronic lead exposure failed to increase PS exposure in erythrocytes with statistical significance although some trends of enhancement were observed. It implies that a certain adaptation might have happened in body during repeated exposure to lead, resulting in attenuation of PS exposure. With this study, we believe that a valuable information was provided for the study on the toxicological significance and the risk assessment of lead contaminated drinking water.     

Interrelationships of glutathione reductase, 5-aminolevulinic acid dehydratase, and free sulfhydryl groups in the erythrocytes of normal and lead-exposed persons

Blood lead, erythrocyte glutathione reductase (GSSG-R), 5-aminolevulinic acid dehydratase (ALA-D), and free sulfhydryl (SH) groups were measured in normal subjects and in those with occupational exposure to lead. With increasing blood lead concentration the activity of GSSG-R rises and that of ALA-D decreases. There is also a fall in the level of free SH with rising blood lead concentrations. There is a high degree of correlation between these parameters, and it is suggested that the changes represent part of a biological control mechanism to compensate for the reduction of available sulfhydryl groups by lead ions.