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单次口服给药后钩吻多组分在猪和大鼠体内的比较毒代动力学特征。

Comparative toxicokinetic profiles of multiple-components of Gelsemium elegans in pigs and rats after a single oral administration.

机构信息

College of Veterinary Medicine, Hunan Agricultural University, 1 Nongda Rd, District Furong, Changsha City, 410128, Hunan, China; Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, 1 Nongda Rd, District Furong, Changsha City, 410128, Hunan, China.

College of Veterinary Medicine, Hunan Agricultural University, 1 Nongda Rd, District Furong, Changsha City, 410128, Hunan, China.

出版信息

Toxicon. 2020 Jul 15;181:28-35. doi: 10.1016/j.toxicon.2020.04.093. Epub 2020 Apr 23.

Abstract

Gelsemium elegans Benth (G. elegans) is highly toxic to humans and rats, but has insecticides and growth promoting effects on pigs and goats. G. elegans is widely used in livestock, but its in vivo dynamics are entirely unknown. Hence, we investigated the toxicokinetic profiles of G. elegans alkaloids after a single oral dose of G. elegans to pigs (1.0 g/kg) and rats (0.1 g/kg). The results indicated that rats were more susceptible to the toxicity of G. elegans than pigs. The toxicokinetic parameters of 22 and 6 components were obtained in pigs and rats, respectively. The components included 9 and 5 gelsedine-type alkaloids in pigs and rats, respectively. The T results of the 5 gelsedine-type alkaloids indicated that these alkaloids were rapidly absorbed in pigs and rats. The T values of the 5 gelsedine-type alkaloids indicated that the elimination rates of these alkaloids in pigs were slower than those in rats. In addition, the C and AUC results indicated that the degrees of absorption and exposure of most alkaloids in pigs were higher than those in rats except GS-2. However, the C value of GS-2 (11-methoxy-14-hydroxygelsenicine) in rats was greater than that of pigs, and the C value of 14-hydroxygelsenicine in pigs was merely greater than 3 times that of rats. The present results suggested that the cause of the toxicological differences species of G. elegans might be related to the degrees of absorption and exposure of gelsedine-type alkaloids, especially for the 14-hydroxygelsenicine and GS-2 in different animals.

摘要

钩吻素子(G. elegans)对人类和大鼠具有高度毒性,但对猪和山羊具有杀虫剂和生长促进作用。钩吻素子在畜牧业中广泛应用,但体内动力学完全未知。因此,我们研究了猪(1.0 g/kg)和大鼠(0.1 g/kg)单次口服钩吻素子后钩吻素子生物碱的毒代动力学特征。结果表明,大鼠比猪更容易受到钩吻素子的毒性影响。分别在猪和大鼠中获得了 22 和 6 个成分的毒代动力学参数。这些成分包括 9 和 5 个钩吻素子型生物碱,分别在猪和大鼠中。5 个钩吻素子型生物碱的 T 结果表明,这些生物碱在猪和大鼠中均迅速吸收。5 个钩吻素子型生物碱的 T 值表明,这些生物碱在猪中的消除速率比在大鼠中慢。此外,C 和 AUC 结果表明,除 GS-2 外,大多数生物碱在猪中的吸收和暴露程度均高于大鼠。然而,GS-2(11-甲氧基-14-羟基钩吻素子)在大鼠中的 C 值大于猪,而猪中 14-羟基钩吻素子的 C 值仅大于大鼠的 3 倍。本研究结果表明,钩吻素子种间毒理学差异的原因可能与钩吻素子型生物碱的吸收和暴露程度有关,特别是对于不同动物中的 14-羟基钩吻素子和 GS-2。

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