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At least 19 recordsLinked to original sources
PubMed1996

Effect of mercuric chloride intoxication and dimercaprol treatment on delta-aminolevulinate dehydratase from brain, liver and kidney of adult mice.

Dimercaprol is a compound used in the treatment of mercury intoxication, however with low therapeutic efficacy. It is assumed that dimercaprol acts by reactivating target sulfhydryl-containing proteins. In the present investigation we studied the inhibitory effect of mercuric chloride treatment (3 days with 2.3 or 4.6 mg/kg HgCl2, sc) in mice on cerebral, renal and hepatic delta-aminolevulinate dehydratase (ALA-D) activity, and a possible reversal of the effect of mercury by dimercaprol (0.25 mmol/kg, 24 hr after the last mercury injection). Mercuric chloride did not inhibit cerebral ALA-D at the doses injected. Dimercaprol treatment did not restore the normal enzyme activity of the liver after the 25% inhibition caused by 4.6 mg/kg HgCl2. In the kidney, dimercaprol enhanced the inhibitory effect of 4.6 mg/kg mercuric chloride (from 35% after mercury treatment alone to 65% after mercury plus dimercaprol treatment). Mercury content increased in kidney after exposure to 2.3 or 4.6 mg/kg and the levels attained were higher than in any other organ Mercury accumulated in liver only after exposure to 4.6 mg/kg HgCl2, and dimercaprol further increased mercury deposition. Dimercaprol treatment also increased the levels of mercury in brain of animals exposed to 4.6 mg/kg HgCl2 The enzymes from all sources presented similar sensitivity to the combined effect of HgCl2 and dimercaprol in vitro. In the absence of preincubation, 0-500 muM dimercaprol potentiated the inhibitory effect of HgCl2 on ALA-D activity. In the presence of preincubation, and 100 and 250 muM dimercaprol enhanced ALA-D sensitivity to mercury, whereas 500 muM dimercaprol partially protected the enzyme from mercury inhibition. Dimercaprol (500 muM) inhibited renal and hepatic ALA-D when preincubated with the enzymes. These data suggested that the dimercaprol-Hg complex may have a more toxic effect on ALA-D activity than Hg2+. Furthermore, the present data show that dimercaprol did not acts by reactivating mercury-inhibited sulfhydryl-containing ALA-D, and that indeed it may have an inhibitory effect per se depending on the tissue.

Analysis of Variance↗
PubMed1988

Intravenous self-administration of elemental mercury: efficacy of dimercaprol therapy.

Deliberate parenteral self-injection of mercury is extremely rare, and is associated with a high degree of mortality and morbidity. Because mercury depresses cellular enzymatic mechanisms by combining with sulfhydryl groups, soluble mercuric salts are toxic to all cells. Embolization of mercury in the lungs has been reported with varying degrees of changes in pulmonary function. Mercury causes urticaria progressing to weeping dermatitis, leukopenia, anemia, diarrhea, salivation, liver damage, and renal damage progressing to acute renal failure with anuria. Dimercaprol is an effective antidote in acute heavy metal intoxication because its two sulfhydryl groups successfully compete with tissue enzyme sulfhydryl groups for the offending metal. Experience with dimercaprol therapy months after the original exposure to mercury is not available. We describe the hospital course of a patient after intravenous elemental injection and the results of dimercaprol therapy months after the original exposure.

Adult↗
PubMed1989

[Myoclonic encephalopathy caused by bismuth salts. Efficacy of treatment with dimercaprol].

Three patients with myoclonic encephalopathy caused by bismuth salts are reported, one with the severe and another with the mild form; dimercaprol was effective for the rapid improvement of the symptoms in both. In one of the patients in whom the clearance of bismuth was calculated it was found to be increased after dimercaprol therapy. We think that dimercaprol is an effective drug for the therapy of myoclonic encephalopathy caused by bismuth salts.

Adult↗
PubMed1982

Effects of hemodialysis and dimercaprol in acute dichromate poisoning.

A 22-month-old infant died after ingesting sodium dichromate his father had brought from work. Treatment included folic acid and dimercaprol administration, hemodialysis, and exchange transfusion. To evaluate this treatment, four dogs were hemodialyzed after receiving intravenous sodium dichromate: their dialyzer chromate clearance was similar to their renal chromate clearance and their dialyzer chromate clearance was not significantly different before or after dimercaprol administration. This and other cases in the literature indicate that although chromate poisoning is often fatal, supportive care, forced diuresis, and chelating agents may be helpful. Hemodialysis may be required if renal failure occurs. Awareness of toxicity and prevention remain the most important approaches.

Acute Disease↗
PubMed1975

Acrylonitrile biotransformation in rats, mice, and chinese hamsters as influenced by the route of administration and by phenobarbital, SKF 525-A, cysteine, dimercaprol, or thiosulfate.

Female wistar rats, conventional albino mice, and Chinese hamsters were given a single dose of acrylonitrile, 0.5 or 0.75 mM/kg body weight. The elimination in the urine of thiocyanate, which is the main metabolite of acrylonitrile, indicated a decreasing proportion of biotransformation after oral (over 20%), intraperitoneal, or subcutaneous (2 to 5%), and intravenous (1%) administration in rats. Oral administration of acrylonitrile in hamsters and mice was also followed by higher biotransformation than intraperitoneal administration. Pretreatment of rats with phenobarbital, SKF 525 A, cysteine, or dimercaprol did not significantly influence elimination of thiocyanate in the urine after the administration of acrylonitrile, but simultaneous administration of thiosulfate significantly increased the metabolized portion of acrylonitrile given intraperitoneally in rats (almost twice) and mice (more than three times). Acrylonitrile was found to be strongly bound in blood. The study confirmed the marked effect of distribution (first-pass metabolic phenomenon) on the metabolic fate of foreign compounds. The strong acrylonitrile binding and cyanoethylation are apparently responsible for the unusually high influence of the different routes of administration on the metabolic fate of acrylonitrile. Acrylonitrile was more effectively metabolized to thiocyanate in mice than in rats after oral, intraperitoneal, and intravenous administration. A greater response of acrylonitrile to thiocyanate metabolism and a larger decrease in its acute toxicity after thiosulfate in mice than in rats indicate possible differences in the mechanism of acrylonitrile toxicity in these animals. Cyanide apparently plays a minor role in the acrylonitrile toxicity in rats, but may play quite an important one in mice.

Administration, Oral↗
PubMed1992

Massive arsenic poisoning--effect of hemodialysis and dimercaprol on arsenic kinetics.

In massive arsenic poisoning, the use of hemodialysis and dimercaprol (BAL) therapy is still controversial. Hemodialysis is thought of value only for supportive care. BAL therapy has been criticized because of its delayed action, its own toxicity and its possible influence on arsenic clearance during hemodialysis. We studied arsenic kinetics during an acute suicidal intoxication (10 g of sodium arsenate). Treatment included gastric lavage, oral charcoal and supportive measures. Hemodialysis was performed immediately and repeated the next day. BAL therapy was prescribed only on the second day. Cardiovascular collapse, anuria and hepatic disturbance recovered in a few days and the patient could be discharged on the 15th day. Instantaneous serum arsenic hemodialysis clearance was 85 +/- 75 ml/min without previous BAL injection and 87.5 +/- 75 ml/min with a previous 250 mg BAL injection (difference not significant) indicating that BAL did not impede arsenic dialysis. The calculated total hemodialysis clearance of arsenic was higher than mean serum hemodialysis clearance indicating that erythrocyte bound arsenic is also eliminated during dialysis. We propose to consider early hemodialysis as an elimination measure in massive arsenic poisoning and to choose BAL as a chelator when dialysis is required.

Adult↗
PubMed1999

Reduction of polysaccharide production in Pseudomonas aeruginosa biofilms by bismuth dimercaprol (BisBAL) treatment.

Microorganisms in biofilms, cells attached to a surface and embedded in secreted insoluble extracellular polymers, are recalcitrant to chemical biocides and antibiotics. When Pseudomonas aeruginosa ERC1 biofilms were treated continuously with 1 x MIC of bismuth dimercaprol (BisBAL), biofilm density determined by both total cell counts and viable cell counts increased during the first 30 h period then decreased thereafter. After 120 h of treatment there was an approximate 3-log reduction in viable cell areal density compared with the untreated control. Per-cell total polysaccharide production was significantly reduced in biofilms exposed to 12.5 microM BisBAL compared with the untreated control. In biofilm cultures, 1 x MIC of BisBAL did not initially kill attached cells but was enough to reduce polysaccharide production. As treatment proceeded, the normalized polysaccharide content was reduced and those cells attached became susceptible to 1 x MIC of BisBAL.

Anti-Bacterial Agents↗
PubMed1999

Surface antigen exposure by bismuth dimercaprol suppression of Klebsiella pneumoniae capsular polysaccharide.

The bacterial capsule is an important virulence determinant in animal and plant disease. Bacterial capsule and slime can be inhibited by bismuth compounds, especially when complexed with lipophilic thiol chelators. Bismuth dimercaprol (BisBAL) at 1 ppm of Bi3+ repressed Klebsiella pneumoniae capsule expression in defined medium by nearly 90%, which exposed subsurface structures. The phagocytic index for BisBAL-treated bacteria increased from <10 to 360 bacteria per 100 neutrophils in the presence of complement and anticapsular or anti-O antigen antiserum. BisBAL treatment also enhanced the reactivity of monoclonal antibodies (MAbs) specific for the O1-antigen lipopolysaccharide (LPS) or the LPS core in a dose-dependent manner as indicated by the results of enzyme-linked immunosorbent assays. When anti-O1 MAb was used, the reactivity increased significantly for fully encapsulated O1:K1 or O1:K2 cells but not for O1:K- cells. Deposition of C3b also increased significantly for BisBAL-treated O1:K1 or O1:K2 cells but not for O1:K- cells. Survival of a serum-sensitive strain was <0.1% when nonimmune human serum absorbed with O1:K1 cells was used and 107% when BisBAL-treated cells were used for absorption. Outer membrane proteins were also more accessible on the surface of K. pneumoniae after BisBAL treatment. Thus, at subinhibitory levels, BisBAL inhibited capsule expression, which promoted phagocytosis, enhanced the reactivity of specific antibodies for LPS O antigen, LPS core epitopes, or outer-membrane proteins, and enhanced complement interaction with encapsulated K. pneumoniae. By unmasking bacterial surface structures and enhancing the immune system reactivity to bacteria, bismuth thiols may prove useful as adjuncts for vaccination.

Animals↗
PubMed1997

Are we ready to replace dimercaprol (BAL) as an arsenic antidote?

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulphonate sodium (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour. 2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication-especially with lipophilic organoarsenicals-may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular availability. 3 This article focuses on aspects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue-bound arsenic in various experimental models, such as monolayers of MDCK (= Madin-Darby canine kidney) cells from dog kidney, isolated perfused liver from guinea-pigs, and perfused jejunal segments from rat small intestine. 4 The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins, DMPS and DMSA may advantageously replace BAL whenever intervention time is not critical. With severe intoxication by organic arsenicals, when the point-of-no-return is a limiting factor, BAL may still have a place as an arsenic antidote.

Animals↗
PubMed1983

Effects of dimercaprol or thioctic acid on the distribution and excretion of Na374AsO3 injected subcutaneously in rats.

This report dealt with the effects of dimercaprol (BAL) and thiotic acid (TA), antidotes against arsenical, on the distribution and the excretion of 74As in several organs of the rat. Each organ was removed and served for quantitative analysis of 74As five days after subcutaneous injection of Na374AsO3 5 microCi/100 g. Administration of BAL or TA was performed intraperitoneally with a single administration or five consecutive administrations for five days before animals were sacrificed. 74As content in each organ of the rat decreased to a greater extent in the five consecutive administration group of BAL or TA than in the non-treated or single administration groups. Moreover, the excretion of 74As in a digestive tract increased more remarkably in the five consecutive administration group than in the non-treated or single administration groups. There were no differences in the excretion or the content of 74As in each organ between the single administration group and the non-treated group.

Animals↗
PubMed1976

Influence of dimercaprol on the early hepatic uptake of 111In-bleomycin in the BALB/c mouse.

Dimercaprol (BAL) administered 1 hr before 111In-bleomycin in the normal BALB/c mouse produced an early preferential hepatic loading of 111In-bleomycin without a loading of the spleen, skin, bone, or muscle. Liver-to-muscle ratios were increased about threefold under the influence of BAL. Liver (c BAL)/liver (s BAL) ratios also increased threefold at 3 hr whereas relative muscle uptake remained at about unity. Indium-111 chloride (colloid, pH 6.5) used as a control did not show a similar increase. The findings suggest that the kinetics and distribution of 111In-bleomycin in the normal BALB/c mouse can be influenced by pretreatment with BAL.

Animals↗