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 combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication

Ameliorative effects of few naturally occurring antioxidants like ascorbic acid (vitamin C), alpha-tocopherol (vitamin E) either alone or in combination with meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA (MiADMSA), on parameters indicative of oxidative stress in the liver, kidney, brain and blood of lead-exposed rats were studied. Male Wistar rats were exposed to 0.1% lead acetate in drinking water for 3 months and treated thereafter with DMSA or its analogue MiADMSA (50 mg/kg, intraperitoneally), either individually or in combination with vitamin E (5 mg/kg, intramuscularly) or vitamin C (25 mg/kg, orally) once daily for 5 days. The effects of these treatments in influencing the lead-induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from the soft tissues were investigated. Exposure to lead produced a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity from 8.44+/-0.26 in control animals to 1.76+/-0.32 in lead control, reduction in glutathione (GSH) from 3.56+/-0.14 to 2.57+/-0.25 and an increase in zinc protoporphyrin level from 62.0+/-3.9 to 170+/-10.7 in blood, suggesting altered haem synthesis pathway. Both the thiol chelators and the two vitamins were able to increase blood ALAD activity towards normal, however, GSH level responded favorably only to the two thiol chelators. The most prominent effect on blood ALAD activity was, however, observed when MiADMSA was co-administered with vitamin C (7.51+/-0.17). Lead exposure produced a significant depletion of hepatic GSH from 4.59+/-0.78 in control animals to 2.27+/-0.47 in lead controls and catalase activity from 100+/-3.4 to 22.1+/-0.25, while oxidized glutathione (GSSG; 0.34+/-0.05 to 2.05+/-0.25), thiobarbituric acid reactive substance (TBARS; 1.70+/-0.45 to 5.22+/-0.50) and glutathione peroxidase (GPx) levels (3.41+/-0.09 to 6.17+/-0.65) increased significantly, pointing to hepatic oxidative stress. Altered, reduced and oxidized GSH levels showed significant recovery after MiADMSA and DMSA administration while, vitamins E and C were effective in reducing GSSG and TBARS levels and increasing catalase activity. Administration of MiADMSA alone and the combined administration of vitamin C along with DMSA and MiADMSA were most effective in increasing hepatic GSH levels to 4.88+/-0.14, 4.09+/-0.12 and 4.30+/-0.06, respectively. Hepatic catalase also reached near normal level in animals co-administered vitamin C with DMSA or MiADMSA (82.5+/-4.5 and 84.2+/-3.5, respectively). Combined treatments with vitamins and the thiol chelators were also able to effectively reduce lead-induced decrease in renal catalase activity and increase in TBARS and GPx level. Combination therapy, however, was unable to provide an effective reversal in the altered parameters indicative of oxidative stress in different brain regions, except in catalase activity. The result also suggests a beneficial role of vitamin E when administered along with the thiol chelators (particularly with MiADMSA) in reducing body lead burden. Blood lead concentration was reduced from 13.3+/-0.11 in lead control to 0.3+/-0.01 in MiADMSA plus vitamin E-treated rats. Liver and kidney lead concentration also showed a most prominent decrease in MiADMSA plus vitamin E co-administered rats (5.29+/-0.16 to 0.63+/-0.02 and 14.1+/-0.21 to 1.51+/-0.13 in liver and kidney, respectively). These results thus suggest that vitamin C administration during chelation with DMSA/MiADMSA was significantly beneficial in reducing oxidative stress however, it had little or no additive effect on the depletion of lead compared with the effect of chelators alone. Thus, the co-administration of vitamin E during chelation treatment with DMSA or MiADMSA could be recommended for achieving optimum effects of chelation therapy.     

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.     

Influence of lead nitrate oń dimethylnitrosamine intoxication

The effect of lead nitrate, an inhibitor of the hepatic drug-metabolizing enzyme system upon the acute hepatotoxicity of dimethylnitrosamine (DMN) was studied.Lead pretreatment significantly prevented polysomal disaggregation induced by the nitrosamine. Cell necrosis, evaluated morphologically and by the release of serum glutamic-pyruvic transaminase (GPT), was also diminised.The metabolism of DMN in rats pretreated with lead nitrate was investigated by following its clearance from blood and by determining, in vitro the demethylation of the nitrosamine. Lead increased, although not significantly, the clearance of DMN from blood, but it lowered the activity of DMN-demethylase 24 h after its administration.Finally, lead lowered the lethal effects of DMN. The mechanism by which lead influenced DMN toxicity is discussed.     

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.     

Yew intoxication in brown bears; a novel approach to diagnosis

Tissues from two juvenile brown bears (Ursus arctos), suspected to have died from yew (Taxus baccata) toxicosis, were chemically examined using thin layer chromatography and high performance liquid chromatography. Extraction and analysis were conducted on heart and liver tissue samples as well as stomach content from the two bears and also on fresh material from an authenticated yew tree which was used as a standard for comparison. The taxine complex comprised of taxine B, 1-deoxytaxine B, isotaxine B, 2-acetyltaxin B, 1-deoxyisotaxine B, 2-acetylisotaxine B, and cinnamates were detected in all extracted samples. taxine B and its isomer isotaxine B are the main toxic constituents in yew. The heart, the target organ of taxine B, is arrested when reaching the lethal tissue concentration of taxine complex. In the present cases, the concentration in the hearts was found to be 37 and 17 μg taxine complex per gram tissue, respectively. As no further absorption into the heart occurs following cardiac arrest, the concentration determined is the actual lethal tissue concentration. Yew ingestion was confirmed by microscopic examination of stomach contents of both bears. Histopathological findings of contraction band necrosis in heart specimens were also consistent with yew 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.     

Modulating effect of Serratula coronata extract on nitric oxide metabolism in the aorta tissues of rats in lead intoxication

Vasotoxic effect of prolonged lead exposures and the efficiency of vasoprotective effect of S. coronata extract per os addition is estimated in rats aorta It is established that lead in aorta causes a significant increase in reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by increasing the activity of inducible isoform of NO-synthase (iNOS). The use of S. coronata extracts promotes ROS and RNS production decreasing by normalyzing the iNOS activity in exposures to lead acetate rat aortas.     

Biochemical changes in blood at lead intoxication and pectin correction

The results of changes in liver biochemical parameters (AST, ALT, alkaline phosphatase, total protein, urea, and bilirubin) indicating the presence and type of liver injury in lead intoxication and subsequent correction with pectin.