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给大鼠、豚鼠和狨猴给药后肾脏和尿液中的梭曼水平。

Soman levels in kidney and urine following administration to rat, guinea pig, and marmoset.

作者信息

de Jong L P, Benschop H P, Due A, Van Dijk C, Trap H C, Van der Wiel H J, Van Helden H P

机构信息

Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.

出版信息

Life Sci. 1992;50(14):1057-62. doi: 10.1016/0024-3205(92)90101-t.

Abstract

Concentrations of C(+/-)P(+/-)-soman (1,2,2-trimethylpropyl methylphosphonofluoridate) in urine of anaesthetized, atropinized and artificially ventilated rats, guinea pigs and marmosets were determined 1-4 h after iv administration of 1-6 LD50 of the agent and in the kidneys 1 h after iv administration of 2-6 LD50 14C-C(+/-)P(+/-)-soman. The concentrations of the toxic C(+/-)P(-)-isomers in both urine and kidneys of the rat were at least two orders of magnitude higher than the corresponding levels in the two other species. Relatively high urine concentrations were also found for C(+/-)P(+/-)-soman-intoxicated (6 LD50) rats pretreated with the nontoxic soman analogue PDP (1,2,2-trimethyl dimethylphosphinate), which considerably decreases the persistence of C(+/-)P(-)-soman in rats, or the carboxylesterase inhibitor CBDP [2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide]. The lethal effect brought about by intravesical administration of C(+/-)P(+/-)-soman in rats showed that the agent can easily be reabsorbed from the bladder. It is concluded, that this reabsorption does probably not explain the previously observed persistence and "late toxicity" of C(+/-)P(+/-)-soman in rats, although the amount of renally excreted C(+/-)P(-)-soman (ca. 1% of the administered dose) should be sufficient for a toxicologically significant effect.

摘要

在对麻醉、已用阿托品处理并进行人工通气的大鼠、豚鼠和狨猴静脉注射1 - 6倍半数致死剂量(LD50)的C(+/-)P(+/-)-梭曼(1,2,2 - 三甲基丙基甲基膦酰氟)1 - 4小时后,以及静脉注射2 - 6倍LD50的14C - C(+/-)P(+/-)-梭曼1小时后,测定了它们尿液中的梭曼浓度,并在1小时后测定了肾脏中的浓度。大鼠尿液和肾脏中有毒的C(+/-)P(-)-异构体的浓度比其他两个物种中的相应水平至少高两个数量级。在用无毒的梭曼类似物PDP(1,2,2 - 三甲基二甲基膦酸酯)预处理的C(+/-)P(+/-)-梭曼中毒(6倍LD50)大鼠的尿液中,也发现了相对较高的浓度,PDP可显著降低C(+/-)P(-)-梭曼在大鼠体内的存留时间,或者在用羧酸酯酶抑制剂CBDP [2 - (邻甲苯基)-4H - 1:3:2 - 苯并二氧磷杂环己二烯 - 2 - 氧化物]处理的大鼠尿液中也发现了较高浓度。大鼠经膀胱内给予C(+/-)P(+/-)-梭曼所产生的致死效应表明,该药剂很容易从膀胱重新吸收。得出的结论是,尽管经肾脏排泄的C(+/-)P(-)-梭曼的量(约为给药剂量的1%)应足以产生毒理学上显著的效应,但这种重新吸收可能无法解释先前观察到的C(+/-)P(+/-)-梭曼在大鼠体内的存留时间和“迟发性毒性”。

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