Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The unicellular alga Poterioochromonas malhamensis was exposed to 12.5 microM of inorganic or triethyl lead and simultaneously treated with lead antidotes and related agents at concentrations of 12.5, 31.25 and 62.5 microM. With increasing concentrations some of the antidotes alone slightly to severely inhibited algal growth (BAL, CaNa2EDTA, EDTA, Na2EDTA), whereas others (DPA, EGTA, DIZO) were non-toxic at the concentrations tested. EGTA and CaNa2EDTA, at all concentrations tested, completely suppressed the growth inhibition caused by inorganic lead; Na2EDTA and EDTA were protective at the lower or medium concentrations, but DIZO, DPA and BAL considerably enhanced lead toxicity with increasing concentrations. None of the tested agents was able to reduce the toxic effects of triethyl lead. All antidotes markedly increased inhibition of algal growth caused by triethyl lead and some were even lethal to the poisoned algae either at the highest (Na2EDTA, EDTA, DPA) or at all concentrations used (DIZO, BAL). P. malhamensis proved to be a highly sensitive and valuable tests system and the results obtained exhibited striking parallels to medical and clinical experience in therapy of human poisoning with inorganic and organic lead compounds.
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PMID:On the toxic effects of tetraethyl lead and its derivatives on the chrysophyte Poterioochromonas malhamensis. IV. Influence of lead antidotes and related agents. 641 29

2,3 dimercaptopropanol (BAL), is a dithiol chelating agent, used for the treatment of heavy metal intoxication; however, this compound has low therapeutic efficacy and in some situations may cause neurotoxic effects. In experimental models, administration of high doses of BAL produces seizures that culminate in animal death. However, investigations on the modulation of neurotransmitter system(s) involved in BAL-induced seizures are still lacking in the literature. In the present study, the neurotoxicity of BAL, as measured by the manifestation of seizures was examined and the modulation of glutamatergic and GABAergic receptors and ion channels potentially involved in BAL-induced seizures was investigated. The results demonstrated that BAL (18.6 mg/kg) induced seizures and all mice died within one day. GABAergic allosteric modulators (3 or 12 mg/kg diazepam and 50 mg/kg phenobarbital) blocked the appearance of seizure and reduced almost completely the death caused by BAL. Carbamazepine (5 mg/kg) significantly reduced the incidence of BAL-induced seizures, while sodium valproate and MK-801 were not effective in reducing the incidence of seizures. Valproate (300 mg/kg) and MK-801(0.5 mg/kg) prolonged the latencies for onset of seizures; however, all animals died within one day after BAL administration. High doses of ZnCl2 (135 mg/kg) blocked the appearance of seizures episodes, but no animal survived more than one day. The content of total non-protein -SH in brain of mice treated with 18.6 and 124 mg/kg BAL increased from 0.9+/-0.3 nmol/g (control animals) to 1.7+/-0.3 and 3.5+/-0.8 nmol/g, respectively. In vitro, 0.1-1 mM concentrations of BAL inhibited [3H]glutamate and [3H]MK-801 binding, but increased the binding of [3H]muscimol to brain synaptic plasma membrane. The results reported here demonstrate that GABAergic allosteric modulators (diazepam and phenobarbital) and carbamazepine, a compound that acts by prolonging the recovery of voltage-activated ion channels from inactivation, are able to abolish BAL-induced seizures, while the NMDA antagonist (MK-801) prolonged the latencies for onset of seizures suggesting that modulators of this subtype of glutamate receptor have a modest role on BAL-induced seizures. The results of the present study suggest that allosteric modulators of GABAergic system and carbamazepine, a voltage-gated Na+-channel antagonist, should be considered for the treatment of animals or patients intoxicated with BAL.
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PMID:Investigations into the mechanism of 2,3-dimercaptopropanol neurotoxicity. 1115 84