Pharmacological prevention of acute lead poisoning in Paramecium.
To understand how lead (Pb2+) and other metals and chelating agents effect living cells, behavioral experiments in the marine ciliate Paramecium calkinsi were carried out. The duration of Backward Swimming Behavior (BSB) of Paramecium was partially reduced when cells were exposed to 100 microM of Ni2+, CD2+ and Co2+. In contrast, Pb2+ increased Paramecium BSB in a dose-dependent manner. Thus, 1, 10, 20, 50 and 100 microM of Pb2+ increased the duration of BSB by 20.4, 83.9, 143.2, 163.2 and 185.2%, respectively. The naphthalenesulphonamide W-7, a calcium channel blocker in lower organisms, abolished the increase of Paramecium BSB initially produced by Pb2+. Paramecium, poisoned with 10 MicroM of Pb2+, were also treated with putative Pb2+ chelating agents, such as meso-2-3-dimercaptosuccinic acid (DMSA), Ca-Na2-EDTA and ascorbic acid. These compounds inhibited the increase of the duration of BSB initially produced by Pb2+ in a dose-dependent manner. The potency of these antidotes in blocking the effects of Pb2+ was as follows: DMSA >> Ca-Na2-EDTA > ascorbic acid. These results provide evidence for a membrane-based mechanism of lead poisoning and support the use of DMSA as a lead antidote.
Bernal
J
J
Departamento de Medicina, Universidad Autńoma de Aguascalientes, México.
Ruvalcaba
S
S
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D002923:Cilia / Q000187:drug effects*; D004492:Edetic Acid / Q000494:pharmacology; D007854:Lead / Q000633:toxicity*; D010247:Paramecium / Q000187:drug effects* / Q000502:physiology; D004113:Succimer / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013550:Swimming / Q000502:physiology; D013997:Time Factors
D000931:Antidotes; D002413:Cations, Divalent; D002614:Chelating Agents; D013449:Sulfonamides; D007854:Lead; C017967:W 7; D004492:Edetic Acid; D004113:Succimer; D001205:Ascorbic Acid