Azure B as a novel cyanide antidote: Preclinical in-vivo studies.
Azure B as a novel cyanide antidote: Preclinical in-vivo studies.
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DOI：
10.1016/j.toxrep.2020.10.015
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发表时间：
2020
影响因子：
--
通讯作者：
Tubbs N
中科院分区：
文献类型：
--
作者：
Haouzi P;McCann M;Tubbs N
4 mg/kg的天青B在未镇静大鼠中是一种非常有效的氰化物解毒剂。天青B对氰化物中毒后呼吸暂停、喘息和心脏骤停有明显的预防作用。在低剂量下，天青B似乎比亚甲蓝更有效。本文研究了亚甲基蓝（MB）的主要脱甲基代谢产物天青B（AzB）对致死性氰化物中毒模型的影响。我们的基本原理如下：AzB 1-具有与MB非常相似的氧化还原性质，这是一种有效的氰化物解毒剂，2-可能比MB具有更高的细胞内扩散性，3-已经存在于MB的市售溶液中，4-在MB给药后很快出现在血液中。因此，AzB可能是治疗氰化物中毒的吩噻嗪生色团家族的成员。我们发现，在自发呼吸的乌拉坦镇静大鼠中，AzB通过增加代谢、通气和心脏收缩力（高达30 - 40 mg/kg）来模拟MB的作用。AzB在60 mg/kg剂量下具有致死毒性。因此，根据这些数据选择AzB的剂量，并且先前用于大鼠中对抗氰化物中毒的MB剂量（4-20 mg/kg）-对应于用于人类治疗高铁血红蛋白血症的剂量。KCN以0.375 mg/kg/min的速度静脉注射13 min，在15 min内100%的未麻醉大鼠死亡。AzB以4 mg/kg（n = 5）或10 mg/kg（n = 5）的剂量在氰化物输注中给药3 min，使100%的动物存活，无临床后遗症。昏迷的发作也明显延迟，没有发生呼吸暂停或喘息。在20 mg/kg剂量下，AzB的效果要差得多。在4 mg/kg时，AzB的解毒作用明显优于相同剂量的MB，与20 mg/kg MB产生的作用没有差异。我们的结论是，AzB是一种有效的氰化物解毒剂在相对较低的剂量。
Azure B at 4 mg/kg is an extremely potent Cyanide antidote in unsedated rats. Azure B was very effective in preventing apnea as well as gasping and cardiac arrest in lethal cyanide intoxication. Azure B appears to be more effective than Methylene blue at low doses. We have determined the effects of azure B (AzB), the main demethylated metabolite of methylene blue (MB), on a model of lethal cyanide intoxication. Our rationale was the following: AzB 1- possesses redox properties very similar to those of MB, which is a potent cyanide antidote, 2- may present a higher intracellular diffusibility than MB, 3- is already present in commercially available solutions of MB, and 4- appears very quickly in the blood after MB administration. AzB could therefore be a member of the phenothiazium chromophore family of interest to treat cyanide intoxication. We found, in spontaneously breathing urethane sedated rats, that AzB mimicked the effects of MB by increasing metabolism, ventilation and cardiac contractility up to 30−40 mg/kg. AzB had a lethal toxicity when the dose of 60 mg/kg was reached. Doses of AzB were therefore chosen in keeping with these data and the doses of MB previously used against cyanide intoxication (4–20 mg/kg) in the rat – doses corresponding to those used in humans to treat methemoglobinemia. KCN, infused at the rate of 0.375 mg/kg/min iv for 13 min, was fatal within 15 min in 100 % of our un-anesthetized rats. AzB at the dose of 4 mg/kg (n = 5) or 10 mg/kg (n = 5) administered 3 min into cyanide infusion allowed 100 % of the animals to survive with no clinical sequelae. The onset of coma was also significantly delayed and no apnea or gasping occurred. At the dose of 20 mg/kg, AzB was much less effective. At 4 mg/kg, the antidotal effects of AzB were significantly better than those produced by MB at the same dose and were not different from the effects produced by 20 mg/kg MB. We conclude that AzB is a potent cyanide antidote at relatively low doses.
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影响因子：
158.5
作者：
BAUD, FJ;BARRIOT, P;BISMUTH, C
通讯作者：
BISMUTH, C
DOI：
10.3109/15563658708992618
发表时间：
1987-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
HALL, AH;DOUTRE, WH;RUMACK, BH
通讯作者：
RUMACK, BH
影响因子：
6.2
作者：
Bebarta VS;Brittain M;Chan A;Garrett N;Yoon D;Burney T;Mukai D;Babin M;Pilz RB;Mahon SB;Brenner M;Boss GR
通讯作者：
Boss GR
影响因子：
6.2
作者：
Bebarta, Vikhyat S.;Pitotti, Rebecca L.;Little, Charles M.
通讯作者：
Little, Charles M.
影响因子：
4.1
作者：
Cambal LK;Weitz AC;Li HH;Zhang Y;Zheng X;Pearce LL;Peterson J
通讯作者：
Peterson J