Influence of organic and inorganic arsenicals on glucose uptake in Madin-Darby canine kidney (MDCK) cells.
The effect of organic (oxophenylarsine; PhAsO) and inorganic (arsenite) arsenicals on the availability of glucose to Madin-Darby canine kidney (MDCK) cells was investigated. The MDCK cells revealed stereospecific D-glucose uptake which was inhibited by both arsenicals in a time- and concentration-dependent manner. After 10 min (37 degrees C), the effects on D-glucose and 2-deoxy-D-glucose accumulation were analogous, suggesting an impaired hexose uptake. With arsenite, 0.5-1 mmol dm-3 were required for half-maximum inhibition (IC50), whereas PhAsO inhibited glucose uptake in the micromolar range (IC50 5-30 mumol dm-3). Under these conditions neither cell morphology nor cellular viability was affected. After 60 min, however, the inhibition of glucose utilization was paralleled by the formation of blebs, detachment of the monolayer and a loss of cellular viability as confirmed by dye exclusion, lactate dehydrogenase and potassium release. It is concluded that inhibition of glucose uptake may contribute to the acute toxicity, especially of organic arsenicals, by further aggravating the depletion of intracellular carbohydrates.
Liebl
B
B
Walther Straub Institute of Pharmacology and Toxicology, Munich, Germany.
Mückter
H
H
Doklea
E
E
Fichtl
B
B
Forth
W
W
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D007668:Kidney; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism
D001152:Arsenicals; D007770:L-Lactate Dehydrogenase; D006593:Hexokinase; D005947:Glucose