Treatment Of Lead Intoxication Research Articles

Effects of combined administration of calcium, iron, zinc, chrysanthemum flavonoids, and DMSA on the treatment of lead intoxication in mice.

The effect of combined administration of calcium (Ca), iron (Fe), zinc (Zn), chrysanthemum flavonoids, and meso-2,3-dimercaptosuccinic acid (DMSA) on the treatment of lead (Pb) intoxication in mice was studied. One hundred ninety female mice (SPF level, aged 18-22 days) were randomly divided into two groups as experimental animals. Mice in group I (10 mice) served as normal control animals, and were administered deionized water containing 12.5 μL/L acetate acid for 6 weeks, whereas mice in group II (180 mice) were exposed to 0.1% (wt/vol) of lead acetate in deionized water for 6 weeks and served as experimental animals. After 6 weeks of successful modeling, 180 mice from group II (lead-exposed) were divided into 18 groups of 10 mice each, 16 of which were treated by the combined administration of Ca, Fe, Zn, chrysanthemum flavonoids, and DMSA by L16 (215 ) orthogonal design. The remaining two groups were given treatment with low and high doses of DMSA, respectively. After three weeks of intervention (ig), the optimal treatment group was identified according to its blood lead level, as well as some antioxidant indices in the blood, liver, and hippocampus. The results indicated that the combined administration of Fe, Zn, chrysanthemum flavonoids, and DMSA with low dosage had the most significant effect on increasing the activities of blood delta-aminolevulinic acid dehydratase and superoxide dismutase (SOD), hepatic SOD and hippocampus nitric oxide synthase while decreasing the blood lead level, the content of hepatic malondialdehyde and hippocampus nitric oxide; this was considered the optimal treatment group. There was no difference in the level of blood hemoglobin between the optimal treatment group and the model control group (the first group of the orthogonal experiment). The activities of blood glutathione (GSH), hepatic GSH and glutathione peroxidase of the optimal treatment group were the same as other groups', and the recovery of the related indexes in the optimal effect group closely resembled the high dosage DMSA group. It can be concluded that the coadministration of Fe, Zn, and chrysanthemum flavonoids along with a low-dose DMSA effectively reduces Pb poisoning and lead-induced oxidative damage in lead-exposed mice; the result may provide a theoretical reference for the treatment of Pb poisoning.

Therapeutic effects of pomegranate (Punica granatum) pith and carpellary membrane extract on lead-induced toxicity in rats

Pomegranate is an ancient edible fruit with various pharmaceutical bioactivities such as antioxidant, lipid regulation and anti-inflammation. In this study the effectiveness of pomegranate pith and carpellary membrane (PPCM) extract in treatment of experimental lead intoxication was assessed in rats. Female Wistar rats were exposed to 1000ppm lead acetate in drinking water for 35 days and treated thereafter with PPCM extiract (100 and 200mg/kg, orally) twice a day for 35 days. The concentration of lead in blood, kidney, liver, bone and brain were measured using atomic absorption spectrophotometry. Treatment with PPCM extract reduced lead retention in blood and tissues. With the highest dose of PPCM extract, the greatest rate of reduction of lead concentrations were observed in brain (61%), blood (53%), and bone (34.5%). No significant changes were observed in copper, zinc and iron concentration of serum and liver, in neither doses of PPCM extract. In conclusion it was demonestrated that PPCM and carpellary membrane had therapeutic effect in the treatment of lead intoxication without any side effects on essential elements in blood and tissues of rats.

The Effect of Vitamin C on the Erythrocyte Antioxidant Enzymes in Intoxicated-Lead Rat Offsprings

Lead exposure or lead poisoning is known to cause a large spectrum of physiological, biochemical, and behavioural disorders in animals. This study was aimed at assessing the effect of vitamin C on the erythrocyte superoxide dismutase, glutathione peroxidase and the glutathione reductase activities in intoxicated- lead rat offsprings. This study was performed on the pups from female Wistar albino rats. The rats were divided into 4 groups and the treatments were administered through drinking water. Group1 (control group) consumed distilled water. Group 2 (lead group) consumed a solution of lead acetate (300mg/L). Group3 (lead + vitamin C) consumed a solution of lead (300mg/L) which was supplemented with vitamin C (2g/L). Group4 (vitamin group) consumed a solution of vitamin C (2g/L). The enzyme activities were determined in all the 4 groups. The administration of lead showed a decrease in the enzyme activities. The superoxide dismutase activity was increased after the administration of lead in combination with vitamin C. The lead treated rats showed significantly lower body weights at birth and at weaning. The vitamin C treatment showed a significant increase in the body weight. The haemoglobin levels were significantly decreased in the lead-treated rats. The addition of vitamin C to the lead treatment and vitamin C alone could elevate the haemoglobin levels significantly. The results of this study showed that lead alterates the erythrocyte antioxidant enzyme activities. There was an increase in the superoxide dismutase activity following the treatment with vitamin C. This study suggests that the treatment with vitamin C during lactation has a therapeutic effect in the treatment of lead intoxication. The administration of vitamin C prevents haemoglobin reduction in the erythrocytes.

S-adenosyl- l-methionine improves impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats

Lead (Pb 2+) exposure in children can induce long-lasting deficits in cognitive function and has been modeled in experimental animals. Based on previous studies which demonstrated that S-adenosyl- l-methionine (SAM) is beneficial in the treatment of lead intoxication, here, we asked the question if SAM treatment could rescue the impaired cognition and synaptic plasticity induced by lead. Rats drank 1500 ppm lead acetate (PbAc) solution or distilled water throughout gestation and lactation. After weaning at postnatal day 22, one half of the control and lead-exposed male offspring were intraperitoneally injected 20 mg SAM/kg daily over a period of 20–22 days. Electrophysiological and Morris water maze test were performed at 44–54 days of age. The result showed that the impaired learning ability induced by lead could be improved significantly by SAM. Furthermore, our results revealed that long-term potentiation (LTP) of excitatory postsynaptic potential and population spike impairments induced by lead were also ameliorated by SAM treatment.

Role of vitamins in treatment of lead intoxication

The efficacy of thiamine, ascorbic acid, and becozinc (a pharmacological preparation containing vitamins of the B-complex group, vitamin C, and zinc) in enhancing excretion and reducing tissue burden of lead and reversing lead-sensitive biochemical alterations was investigated in lead pre-exposed rat. These vitamins were effective in mobilizing lead from blood, liver, and kidney into urine and/or feces and in restoring partially blood zinc protoporphyrin level. All the vitamins were effective in reversing completely the lead-induced increase in blood and renal calcium levels, and becozinc was particularly effective in restoring the decreased hepatic and tibia zinc content. However, the inhibition of blood δ-aminolevulinic acid dehydratase activity and increase in urinary aminolevulinic acid excretion due to lead remained uninfluenced, which may require more time for recovery. The results suggest the use of becozinc as a safe alternate to treatment of lead poisoning with the chelating agents. J. Trace Elem. Exp. Med. 13:305–315, 2000. © 2000 Wiley-Liss, Inc.

Mobilization of lead by calcium versenate and dimercaptosuccinate in the rat.

1. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) individually and in permutation-combination in various doses (0.1, 0.2 and 0.4 mmol/kg bodyweight) were investigated for their efficacy to mobilize lead from vital tissues into urine and faeces and to restore the lead-sensitive biochemical parameters in lead pre-exposed rats with a view to develop the most acceptable treatment regimen for lead poisoning with a minimal loss of endogenous essential elements. 2. The combined therapy was more effective than a single chelator treatment. 3. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA caused a lower depletion of zinc, calcium and iron but possessed almost equal capability to that of 0.4 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA to produce urinary as well as faecal excretion of lead, to reduce the tissue burden of lead, including that of the brain, and to reverse lead-induced biochemical alterations. 4. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA has shown a definite improvement over previously reported combinations in terms of removal of lead from tissues, particularly the brain, restoration of urinary delta-aminolevulinic acid levels and a decrease in the loss of body zinc and is, therefore, recommended for the treatment of lead intoxication.

Role of Chelating Agents for Prevention, Intervention, and Treatment of Exposures to Toxic Metals

Role of Chelating Agents for Prevention, Intervention, and Treatment of Exposures to Toxic Metals

Lead intoxication in an anuric patient: management by intraperitoneal EDTA

Treatment of lead intoxication with intravenous ethylene-diamine-tetra-acetic acid (EDTA) depends on the urinary excretion of chelated lead. This route of excretion was absent in a 48-year-old patient with childhood lead exposure and end stage renal failure who developed encephalopathy and a rapidly progressive neuropathy thought to be due to acute lead intoxication. Diagnosis was confirmed by lead chelation with EDTA and neurophysiological studies. EDTA was added by the patient to her chronic ambulatory peritoneal dialysis (CAPD) fluid each week and chelated lead excreted in the dialysate. Intraperitoneal administration of EDTA was 70% as efficient in removing lead as intravenous administration. Four months of home chelation therapy was associated with resolution of the encephalopathy but no improvement in the peripheral neuropathy.

Teratogenic effect of calcium edetate (CaEDTA) in rats and the protective effect of zinc

The calcium chelate of EDTA (CaEDTA) currently is the drug of choice in the treatment of lead intoxication. This study investigated the teratogenic potential of CaEDTA, administered parenterally during periods of organogenesis and determined if incorporating zinc into EDTA would protect against teratogenic effects. Four doses (2, 4, 6, and 8 mmol/m 2/day) of CaEDTA, two concentrations (8 and 20 mmol/m 2/day) of ZnEDTA and ZnCaEDTA (molar ratio 0.5:0.5:1) were used, and a saline control (0.9% NaCl). Timed-pregnant Long-Evans rats were assigned at random to the treatment groups, 20 per dose for each chelate and 30 to the saline control. Rats were injected with the chelate or saline solution sc, twice daily during the 11th through 15th days of gestation. Pups removed by cesarean section on the 21st day were processed for osseous and visceral examination. Additional animals per treatment group were used for maternal plasma and liver and fetal zinc determinations. Results showed increases in several abnormalities (submucous cleft, cleft palate, adactyly-syndactyly, curly tail, abnormal rib and vertebrae) with increasing amounts of CaEDTA. No malformations were seen with ZnEDTA at either dose or with ZnCaEDTA at 8 mmol/m 2/day. However, submucous cleft was seen in 6 of 20 litters from the dams receiving the higher dose of ZnCaEDTA. It was concluded that CaEDTA is teratogenic in rats at concentrations which, except for decreased weight gain, produce no discernible toxicity to the dam, and which are comparable to the recommended therapeutic dosage in humans (1500 mg/m 2/day corresponding to 4 mmol/m 2/day). Protection is afforded by incorporating zinc in the chelate.

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.

Beneficial effect of S-adenosyl- l-methionine in lead intoxication. Another approach to clinical therapy

1. 1. Five patients with chronic lead intoxication were treated with S-adenosyl- l-methionine (12 mg/kg body weight, daily), given intravenously, over a period of 22 days. 2. 2. A significant recovery of erythrocytic ALA-D was observed in all cases, after therapy. 3. 3. Blood lead content significantly pathologic at the beginning of SAM administration, rapidly decreased within 24–48 h of initiating treatment, reaching nearly control values at the end of the trial. 4. 4. A good correlation between recovery of ALA-D activity and decreased concentration of lead in RBC was found. 5. 5. GSH content in blood was diminished in lead poisoned patients, increasing to normal levels after SAM administration. 6. 6. Other biochemical parameters such as Deaminase activity in RBC, ALA, PBG, porphyrins and lead in urine and serum γ-GT were measured, showing no important deviations from control values before, during or after treatment. 7. 7. Both biochemical and clinical improvement was observed, indicating that SAM therapy is beneficial in the treatment of lead intoxication. No untoward signs were observed. 8. 8. The mechanism of action of SAM is not yet clear; however, a chelating effect could be excluded, and very likely its action can be attributed to glutathione availability.

Treatment of Lead Intoxication

Treatment of Lead Intoxication

Treatment of lead intoxication. Combined use of peritoneal dialysis and edetate calcium disodium.

Four patients suffering from lead intoxication due to consumption of illicitly distilled alcohol were given small doses of edetate calcium disodium (Calcium Disodium Versenate) and then subjected to peritoneal dialysis. The rate of deleading by dialysis exceeded significantly the rate of urinary lead excretion in each patient. In each patient, the administration of edetate calcium disodium induced an increase in the amount of lead recovered in the dialysate.

The Metabolism of Lead in Man in Health and Disease.

More than 35 years ago Aub and associates of Harvard published a monograph on lead poisoning, which was judged the definitive work in this field for a number of years. In the intervening time, Robert Kehoe of the Kettering Laboratory, the University of Cincinnati, has devoted essentially a professional lifetime to the same problem. Since lead is an important heavy metal in current economy and environment, it is imperative that this subject be continually surveyed as a major problem for investigation. The breadth of study must inevitably include normal and nontoxic levels of metabolism of lead in man, plants, and animals, as well as the exposure of man especially to toxic concentrations. And lastly, a comprehensive study must include the treatment of lead intoxication from excessive primary intake or secondarily from absorption by plants and animals. The Harben Lectures review the potential industrial hazards as well as lead inhalation from