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香叶醇在绵羊体内的药理学特性及其在控制胃肠道线虫方面的潜在用途。

Pharmacological characterization of geraniol in sheep and its potential use in the control of gastrointestinal nematodes.

作者信息

Miró María Victoria, Costa-Júnior Livio Martins, Alvarez Luis Ignacio, Lanusse Carlos, Virkel Guillermo, Lifschitz Adrián

机构信息

Centro de Investigación Veterinaria de Tandil (CIVETAN) CONICET-CICPBA-UNCPBA, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Paraje Arroyo Seco S/N, Campus Universitario, Tandil, Argentina.

Laboratory of Parasite Control, Department of Pathology, Center for Biological and Health Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, São Luis, Brazil.

出版信息

Vet Anim Sci. 2022 Sep 14;18:100269. doi: 10.1016/j.vas.2022.100269. eCollection 2022 Dec.

Abstract

Geraniol (GNL) was effective against gastrointestinal nematodes ; nevertheless, the anthelmintic effect of phytochemicals combined with synthetic drugs has been little explored . This article characterized / the pharmacological features of GNL in sheep as well as its pharmacokinetic interaction with albendazole (ABZ). Additionally, the efficacy of GNL against was evaluated in lambs. Liver microsomes from lambs were incubated in the absence or presence of GNL to analyze CYP1A1, CYP1A2 and FMO metabolic pathways. The effect of GNL on the hepatic sulfoxidation and sulfonation of ABZ and the ruminal sulforeduction of albendazole sulfoxide (ABZSO) was assessed. The pharmacokinetic interaction of ABZ and GNL was evaluated in lambs. The effect of GNL on the fecal egg count was evaluated in lambs infected with a resistant isolate of . In sheep liver microsomes, the presence of 2 mM GNL reduced the CYP1A1, CYP1A2 and FMO pathways by 77.9, 90.8 and 84.5%, respectively, with respect to control (P < 0.05). In the presence of 2 mM GNL, the ABZ sulfoxidation decreased from 114.4 ± 8.49 (control) to 50.24 ± 11.1 nmol/min.mg, and ABZSO production decrease from 0.52 ± 0.14 to 0.09 ± 0.03 nmol/h.mg. No changes in the pharmacokinetic behavior of ABZ were observed in the presence of GNL. The efficacy of four doses of GNL was 40.5%. These findings highlight the importance of integrated pharmaco-parasitological studies to develop new pharmacological tools for controlling gastrointestinal parasites.

摘要

香叶醇(GNL)对胃肠道线虫有效;然而,植物化学物质与合成药物联合使用的驱虫效果尚未得到充分研究。本文描述了GNL在绵羊体内的药理学特性及其与阿苯达唑(ABZ)的药代动力学相互作用。此外,还评估了GNL对羔羊的疗效。在不存在或存在GNL的情况下孵育羔羊的肝微粒体,以分析CYP1A1、CYP1A2和FMO代谢途径。评估了GNL对ABZ肝氧化和磺化以及阿苯达唑亚砜(ABZSO)瘤胃还原的影响。在羔羊中评估了ABZ和GNL的药代动力学相互作用。评估了GNL对感染耐药分离株的羔羊粪便虫卵计数的影响。在绵羊肝微粒体中,相对于对照,2 mM GNL的存在分别使CYP1A1、CYP1A2和FMO途径降低了77.9%、90.8%和84.5%(P < 0.05)。在2 mM GNL存在下,ABZ氧化从114.4±8.49(对照)降至50.24±11.1 nmol/min.mg,ABZSO生成从0.52±0.14降至0.09±0.03 nmol/h.mg。在存在GNL的情况下,未观察到ABZ药代动力学行为的变化。四剂GNL的疗效为40.5%。这些发现突出了综合药物寄生虫学研究对于开发控制胃肠道寄生虫的新药理学工具的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f27/9486669/d086e63a1f52/gr1.jpg

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