Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model

Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model
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DOI:
10.1177/096032719601500104
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发表时间:
1996-01-01
影响因子:
2.8
通讯作者:
Baud, FJ
Baud, FJ
中科院分区:
医学4区
文献类型:
--
作者:
Astier, A;Baud, FJ

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1羟钴胺作为氰化物中毒解毒剂的合理性是基于CN离子对钴化合物的高亲和力。在人成纤维细胞与500 mU[C-14]氰化物孵育10分钟后,在37℃(10.45+/-1.51 mm)和4℃时的累积倍数分别为25和11.9。5min),提示该过程为一级反应(k=0.25min(-1))。5在500 mU M的uchbl与成纤维细胞孵育后,细胞内氰化物减少了75%,并伴随着细胞内氰钴胺CNCbl的形成(细胞内外比:158)。6这些结果表明,uchb1能够穿透大量氰化物负载的细胞,并将氰化物络合成无毒的CNCb1形式。
1 The rational for administering hydroxocobalamin (OHCbl) as an antidote to cyanide poisoning is based on the high affinity of CN ion for cobalt compounds. However, only few data are available on the influence of OHCbl on the intracellular cyanide pool.2 In human fibroblasts incubated for 10 min with 500 mu M of [C-14] cyanide, the accumulation ratio was 25 at 37 degrees C (10.45 +/- 1.51 mM) and 11.9 at 4 degrees C.3 Using the monoblastic U-937 cell line, a rapid uptake of radioactive cyanide was observed with a maximum accumulation ratio of 1.97 at 5 min.4 A linear relationship between cyanide uptake by U-937 cells and cyanide concentration in incubation medium (10-500 mu M; 5 min) was found suggesting a first order process (k=0.25 min(-1)).5 After incubation of fibroblasts with 500 mu M of OHCbl, a 75% decrease of intracellular cyanide was observed, with concomittant formation of intracellular cyanocobalamin CNCbl (intracellular/extracellular ratio: 158).6 These findings suggest that OHCbl is able to penetrate into heavily cyanide loaded cells and to complex cyanide to the non-toxic CNCbl form.