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鸽子体内[具体物质未给出]对顺铂诱导呕吐的抑制作用:神经化学证据

Suppression of Cisplatin-Induced Vomiting by in Pigeons: Neurochemical Evidences.

作者信息

Ullah Ihsan, Subhan Fazal, Alam Javaid, Shahid Muhammad, Ayaz Muhammad

机构信息

Department of Pharmacy, University of Swabi, Swabi, Pakistan.

Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.

出版信息

Front Pharmacol. 2018 Mar 16;9:231. doi: 10.3389/fphar.2018.00231. eCollection 2018.

Abstract

(, family ) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigate for potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period. hexane fraction (HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% ( < 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction ( < 0.05). At acute time point (3 h), CS-HexFr decreased ( < 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18 h (delayed time point) CS-HexFr attenuated ( < 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema. -HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect of -HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3 and 18 h in pigeons.

摘要

(某物质,家族)在动物模型和临床中已被报道具有针对癌症化疗引起的呕吐的止吐活性。当前的研究旨在调查其对减轻健康鸽子顺铂诱导的呕吐的潜在有效性,并研究其对呕吐行为中涉及的中枢和外周神经递质的影响。使用配备电化学检测器的高效液相色谱系统对神经递质5-羟色胺(5HT)、多巴胺(DA)及其代谢产物;二羟基苯乙酸(Dopac)、高香草酸(HVA)和5-羟基吲哚乙酸(5HIAA)在特定脑区(最后区和脑干)的中枢以及小肠的外周进行定量。顺铂(7mg/kg静脉注射)在24小时观察期内诱导呕吐但无致死性。某物质的己烷馏分(HexFr;10mg/kg)减轻了顺铂诱导的呕吐约65.85%(P<0.05);参考止吐药物甲氧氯普胺(MCP;30mg/kg)使呕吐减少约43.90%(P<0.05)。在急性时间点(3小时),CS-HexFr降低(P<0.001)了最后区、脑干和小肠中5HT和5HIAA的浓度,而在18小时(延迟时间点),CS-HexFr减弱(P<0.001)了顺铂在脑干和小肠中引起的5HT以及最后区中多巴胺的升高。单独的HexFr处理除了显著降低的5HIAA和HVA外,未改变脑区和小肠中的基础神经递质及其代谢产物。总之,HexFr的止吐作用是通过在两个不同时间点,即鸽子的3小时和18小时,以混合方式由抗5-羟色胺能和抗多巴胺能成分介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e621/5865282/d9d8fdfccf34/fphar-09-00231-g001.jpg

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