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首页> 外文期刊>Archives of Toxicology >Comparative antidotal efficacy of benzylpenicillin, ceftazidime and rifamycin in cultured human hepatocytes intoxicated with α-amanitin
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Comparative antidotal efficacy of benzylpenicillin, ceftazidime and rifamycin in cultured human hepatocytes intoxicated with α-amanitin

机译：苄青霉素，头孢他啶和利福霉素在人α-阿马尼汀中毒的培养人肝细胞中的比较解毒功效

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The most often used antidote to treat poisoning caused by amanitin-containing mushrooms is benzylpenicillin (BPCN). However, a very few reports suggest that other antibiotics such as ceftazidime (CEFT) and rifamycin SV (RIFSV) show better antidote activity against amanitins than BPCN. Given this, there is an ongoing debate as which of three antidotes is optimal for treatment of such poisonings. In this study, the efficacy of BPCN was compared with those of CEFT and RIFSV in human hepatocyte model. The functional integrity and viability of cultured hepatocytes was evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and by measurements of lactic dehydrogenase (LDH) activity. In the first experimental layout, hepatocytes were simultaneously exposed to α-AMA and tested antidotes, while in the second layout, the cells were exposed for the first 12 h to α-AMA only, and then, the medium containing α-AMA was exchanged to culture medium containing both α-AMA and the antidotes tested. The results demonstrated that simultaneous administration of α-AMA and each of tested antidotes (BPCN, CEFT, RIFSV) effectively protected human hepatocytes; however, in the group dosed with BPCN, the highest hepatocyte viability was observed. In cell cultures from experimental layout II, all tested antidotes were ineffective, which indicates that after the critical dose of α-AMA had been taken up by hepatocytes, further suppression of this process does not protect the cells against injury. Thus, 12 h of exposure of incubated hepatocytes to α-AMA is a sufficient time for such a cellular uptake of a critical dose of this toxin. In summary, it can be concluded that easily accessible and low-cost BPCN should be widely used as an antidote against amanitins. However, the key to successful therapy is a quick implementation of an antidote in order to protect as large as possible portion of the liver parenchyma against the devastating uptake of a critical dose of amanitins.
机译：治疗含金刚霉素蘑菇引起的中毒的最常用解毒剂是苄青霉素（BPCN）。但是，极少有报道表明，头孢他啶（CEFT）和利福霉素SV（RIFSV）等其他抗生素对甘露素的解毒活性比BPCN更好。鉴于此，目前正在进行辩论，因为三种解毒剂中的哪一种最适合治疗此类中毒。在这项研究中，将BPCN与CEFT和RIFSV在人肝细胞模型中的功效进行了比较。使用MTT [3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑鎓]测定并通过测量乳酸脱氢酶（LDH）活性来评估培养的肝细胞的功能完整性和生存能力。在第一个实验布局中，将肝细胞同时暴露于α-AMA和测试的解毒剂，而在第二个实验布局中，将细胞仅在前12 h暴露于α-AMA，然后更换含有α-AMA的培养基含有α-AMA和解毒剂的培养基。结果表明，同时施用α-AMA和每种被测解毒剂（BPCN，CEFT，RIFSV）均能有效保护人肝细胞。但是，在服用BPCN的组中，观察到最高的肝细胞活力。在实验布局II的细胞培养物中，所有测试的解毒剂均无效，这表明在关键剂量的α-AMA被肝细胞吸收后，对该过程的进一步抑制不能保护细胞免受损伤。因此，将培养的肝细胞暴露于α-AMA12小时足以使细胞摄取临界剂量的这种毒素。综上所述，可以得出结论，容易获得且价格低廉的BPCN应该被广泛用作抗金刚素的解毒剂。但是，成功治疗的关键是快速使用解毒剂，以保护尽可能多的肝实质免受关键剂量的甘露糖素的破坏性吸收。

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