Gossypol-induced free radical toxicity to isolated islet cells.
1. The cytotoxicity of the polyphenolic potential male antifertility agent gossypol was investigated on isolated mouse islets cells. 2. Gossypol shared many properties with the diabetogenic agent alloxan. 3. Gossypol (0.1-1.0 mmol/l) induced a concentration-dependent increase of Trypan Blue uptake by the cells, indicating an increase of membrane permeability to the dye. 4. Trypan Blue uptake induced by 0.5 mmol/l gossypol was inhibited by concomitant incubation of the cells with enzymatic (200 mg/l superoxide dismutase, 200 mg/l catalase, 3 mmol/l cytochrome-c), or low-molecular weight (50 mmol/l D-mannitol) scavengers of oxygen radicals, and the metal chelator diethylenetriaminepentacetic acid (DTPA) (50 mumol/l). 5. The results support the hypothesis that gossypol is B-cytotoxic by generation of noxious free radicals and that when proposing gossypol as a male antifertility agent, studies to exclude gossypol as a diabetogenic agent should first be performed in vivo.
Grankvist
K
K
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
D000818:Animals; D002478:Cells, Cultured; D005609:Free Radicals; D006072:Gossypol / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D010100:Oxygen / Q000633:toxicity; D014343:Trypan Blue
D005609:Free Radicals; D014343:Trypan Blue; D006072:Gossypol; D010100:Oxygen