Influence of glucose on the toxicity of oxophenylarsine in MDCK cells.
Trivalent arsenicals like oxophenylarsine (PhAsO) inhibit cellular pyruvate dehydrogenase, thus leading to a drop of acetylCoA formation and a slow-down of the citric acid cycle. Glucose may protect cells from arsenic toxicity, because increased glycolysis may prevent fatal shortage of ATP. On the other hand, PhAsO has been shown to inhibit glucose uptake in Madin-Darby canine kidney (MDCK) cells. We have investigated the effect of PhAsO on viability, ATP levels and glucose uptake of MDCK cells in the presence of normal (5 mmol/l) and low (0.01 mmol/l) glucose concentrations. At normal as well as at low glucose concentrations, cell viability as assessed by formazan formation was not affected by PhAsO concentrations up to 2 mumol/l within 3 h of observation. At higher PhAsO concentrations viability was diminished earlier and more pronounced in the presence of low glucose concentrations. 10 mumol/l PhAsO induced a drastic drop of ATP within 30 min which was followed by an almost complete loss of viable cells after 180 min in the presence of low glucose concentrations, while at normal glucose levels no influence on ATP contents or on cell viability was detected within 60 min of incubation. On the other hand, glucose uptake, determined as 14C accumulation by cells incubated for 10 min with D-[6-14C]-glucose, was inhibited by PhAsO at low as well as at normal glucose concentrations in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020261:Arsenic Poisoning; D001152:Arsenicals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*
D001152:Arsenicals; D004791:Enzyme Inhibitors; D011768:Pyruvate Dehydrogenase Complex; C029341:oxophenylarsine; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D005947:Glucose