Liebl B, Mückter H, Doklea E, Reichl F X, Fichtl B, Forth W
Walther-Straub-Institut für Pharmakologie and Toxikologie, Universität München, Germany.
Arch Toxicol. 1995;69(6):421-4. doi: 10.1007/s002040050194.
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)
三价砷化合物如氧苯胂（PhAsO）可抑制细胞丙酮酸脱氢酶，从而导致乙酰辅酶A生成减少，柠檬酸循环减缓。葡萄糖可保护细胞免受砷毒性影响，因为糖酵解增加可防止ATP致命性短缺。另一方面，已表明PhAsO可抑制马-达二氏犬肾（MDCK）细胞对葡萄糖的摄取。我们研究了在正常（5 mmol/L）和低（0.01 mmol/L）葡萄糖浓度下，PhAsO对MDCK细胞活力、ATP水平及葡萄糖摄取的影响。在正常及低葡萄糖浓度下，通过甲臜形成评估的细胞活力在观察3小时内不受高达2 μmol/L的PhAsO浓度影响。在较高PhAsO浓度下，低葡萄糖浓度时细胞活力更早且更显著地降低。10 μmol/L PhAsO在30分钟内导致ATP急剧下降，在低葡萄糖浓度下，180分钟后几乎所有活细胞丧失，而在正常葡萄糖水平下，孵育60分钟内未检测到对ATP含量或细胞活力的影响。另一方面，通过用D-[6-14C]-葡萄糖孵育10分钟的细胞对14C的积累来测定的葡萄糖摄取，在低葡萄糖浓度和正常葡萄糖浓度下均被PhAsO以剂量依赖方式抑制。（摘要截短于250字）
