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恩诺沙星在彭泽鲫脑与外周组织中的代谢及残留差异以及由此导致的脑损伤

Metabolism and residue differences of Enrofloxacin between the brain and peripheral tissues and the resulting brain damages in crucian carp (Carassius auratus var. Pengze).

作者信息

Wan Gen, Zhang Fan, Wang Runping, Wei Lili, Huang Jianzhen, Lu Xinmin, Cai Zhihuan, Wang Long, Zhong Zhiwei, Xu Yanyan, Ruan Jiming

机构信息

Department of Aquaculture, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Bureau of Agriculture and Rural Affairs of Ganzhou City, Ganzhou, China.

出版信息

J Vet Pharmacol Ther. 2023 Jan;46(1):42-51. doi: 10.1111/jvp.13092. Epub 2022 Sep 11.

DOI:10.1111/jvp.13092
PMID:36089776
Abstract

This study aimed to explore the metabolism and residue differences of Enrofloxacin (ENR) at two doses between the brain and peripheral tissues (liver, kidney, and muscle) along with the brain damages caused by ENR in crucian carp (Carassius auratus var. Pengze). The concentrations of ENR in tissues were determined using a validated high-performance liquid chromatography (HPLC) analysis. Relying on the hematoxylin-eosin (HE) staining method, brain damages caused by the drug were evaluated by the section of pathological tissue. Metabolism and residue results showed that ENR could be detected in the brain throughout the experiment both at median lethal dose (LD at 96 h, 1949.84 mg/kg) and safe dose (SD, 194.98 mg/kg), as well as in the three peripheral tissues. The maximum residue at LD followed the decreasing order of liver >kidney > brain > muscle. Although the C of ENR at SD in the brain was significantly lower than that in other peripheral tissues (p < .05), it still reached 41.91 μg/g. The T of ENR in brain tissue at the same dose was both shorter than that in peripheral tissues. At LD , the amount of ENR residues in brain was lower than that in peripheral tissues on the whole, except that it had been higher than in the muscle for the first 3 h. At SD, the drug residue in brain tissue was lower than that in peripheral tissues from 12 h to 960 h, but it exceeded the muscle and kidney at 1 h and 6 h, respectively. At 960 h, the residual amount of ENR at SD in the brain was 0.09 μg/g, while it was up to 0.15 μg/g following the oral administration at LD . Demonstrated by the HE staining, there were pathological lesions caused by ENR in the brain at LD , which were characterized by sparse neural network and increased staining of glial cells. The present results indicated that metabolism and residue of ENR in crucian carp were affected by the tissue type and drug dosage, and the ENR could also bring about histopathological changes in the brain.

摘要

本研究旨在探讨恩诺沙星(ENR)在两种剂量下,彭泽鲫脑组织与外周组织(肝脏、肾脏和肌肉)之间的代谢和残留差异,以及恩诺沙星对彭泽鲫脑组织造成的损伤。采用经过验证的高效液相色谱(HPLC)分析法测定组织中恩诺沙星的浓度。依靠苏木精-伊红(HE)染色法,通过病理组织切片评估药物对脑组织造成的损伤。代谢和残留结果表明,在整个实验过程中,恩诺沙星在半数致死剂量(96小时LD,1949.84毫克/千克)和安全剂量(SD,194.98毫克/千克)下均可在脑组织以及三种外周组织中被检测到。LD下的最大残留量依次为肝脏>肾脏>脑>肌肉。尽管SD下脑组织中恩诺沙星的C显著低于其他外周组织(p<0.05),但仍达到41.91微克/克。相同剂量下,脑组织中恩诺沙星的T均短于外周组织。在LD下,脑组织中恩诺沙星的残留量总体低于外周组织,只是在最初3小时高于肌肉组织。在SD下,脑组织中的药物残留量在12小时至960小时低于外周组织,但在1小时和6小时分别超过了肌肉和肾脏组织。在960小时时,SD下脑组织中恩诺沙星的残留量为0.09微克/克,而LD口服给药后高达0.15微克/克。HE染色显示,LD下恩诺沙星可导致脑组织出现病理损伤,其特征为神经网络稀疏和神经胶质细胞染色增强。目前的结果表明,彭泽鲫体内恩诺沙星的代谢和残留受组织类型和药物剂量的影响,且恩诺沙星还可引起脑组织的组织病理学变化。

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