Ascorbate-induced free radical toxicity to isolated islet cells.
Ascorbate is known to be cytotoxic by generating free oxygen radicals, a property shared with the diabetogenic drug alloxan. Some reports indicate that also ascorbate may be diabetogenic. In this study the cytotoxicity of ascorbate on isolated mouse islet cells has been investigated. Ascorbate (0.5-2.0 mmol/l) induced a concentration-dependent increase of trypan blue uptake by the cells, indicating an increase of membrane permeability to the dye. Trypan blue uptake induced by 2.0 mmol/l ascorbate was inhibited by concomitant incubation of the cells with 200 mg/l superoxide dismutase, 200 mg/l catalase, 3.0 mmol/l cytochrome-c or 50 mumol diethylenetriaminepentacetic acid (DTPA), but not by 50 mmol/l D-mannitol. The results indicate that ascorbate is cytotoxic to islet cells by metal-catalysed free radical generation.
Andersson
M
M
Department of Clinical Chemistry, Umeå University, Sweden.
Grankvist
K
K
D000496:Alloxan / Q000633:toxicity; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008353:Mannitol; D051379:Mice; D004369:Pentetic Acid / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014343:Trypan Blue / Q000378:metabolism
D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D005609:Free Radicals; D008353:Mannitol; D000496:Alloxan; D004369:Pentetic Acid; D013482:Superoxide Dismutase; D014343:Trypan Blue; D001205:Ascorbic Acid