Rubidium uptake by mouse pancreatic islets exposed to 6-hydroxydopamine, ninhydrin, or other generators of hydroxyl radicals.
The purpose was to study the toxicity of drugs known to generate free radicals on isolated pancreatic islets. The accumulation of 86Rb+ by mouse pancreatic islets was measured in vitro. Exposing the islets to 6-hydroxydopamine, ninhydrin, or phenazine methosulphate+NADH inhibited the Rb+ uptake, whereas paraquat or acetylphenylhydrazine had no effect. This effect of 6-hydroxydopamine was prevented by either of the hydroxyl radical scavengers, sodium benzoate and mannitol, but not by the non-scavenger, urea; ninhydrin was partially protected against by mannitol but not by benzoate. Protection against 6-hydroxydopamine was also afforded by D-glucose but not by L-glucose or 3-O-methyl-D-glucose; none of the sugars protected against ninhydrin. In damaging islet beta-cells and in being protected against by D-glucose, 6-hydroxydopamine closely resembles the diabetogenic drug, alloxan. It is suggested that protection against alloxan may involve both glucose metabolism and the interaction of glucose with its membrane-located carrier, while protection against 6-hydroxydopamine appears to be unrelated to the hexose carrier mechanism.
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D005260:Female; D005609:Free Radicals; D005947:Glucose / Q000494:pharmacology; D006878:Hydroxides / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D009555:Ninhydrin / Q000494:pharmacology*; D016627:Oxidopamine; D012413:Rubidium
D001565:Benzoates; D005609:Free Radicals; D006878:Hydroxides; D006892:Hydroxydopamines; D007192:Indenes; D008773:Methylphenazonium Methosulfate; D008353:Mannitol; D016627:Oxidopamine; D009555:Ninhydrin; D005947:Glucose; D012413:Rubidium