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子宫内氟喹诺酮暴露不会影响所产驹驹的关节软骨。

Fluoroquinolone exposure in utero did not affect articular cartilage of resulting foals.

机构信息

Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, IL, USA.

Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, IL, USA.

出版信息

Equine Vet J. 2021 Mar;53(2):385-396. doi: 10.1111/evj.13295. Epub 2020 Jul 20.

Abstract

BACKGROUND

Recent studies have shown that fluoroquinolones, specifically, enrofloxacin and its active metabolite (ciprofloxacin), cross the equine placenta without causing gross or histological lesions in the first and third trimester fetuses or resulting foal. However, it is possible that in utero exposure to fluoroquinolones may cause subtle lesions not detectable by standard means; thus, a more in-depth assessment of potential toxicity is warranted.

OBJECTIVES

To use quantitative magnetic resonance imaging (qMRI), biomechanical testing, and chondrocyte gene expression to evaluate the limbs of foals exposed to enrofloxacin during the third trimester of pregnancy.

STUDY DESIGN

In vivo and control terminal experiment.

METHODS

Healthy mares at 280 days gestation were assigned into three groups: untreated (n = 5), recommended therapeutic (7.5 mg/kg enrofloxacin, PO, SID, n = 6) or supratherapeutic (15 mg/kg, PO, SID, n = 6) doses for 14 days. Mares carried and delivered to term and nursed their foals for ~30 days. Two additional healthy foals born from untreated mares were treated post-natally with enrofloxacin (10 mg/kg PO, SID, for 5 days). By 30 days, foal stifles, hocks, elbows, and shoulders were radiographed, foals were subjected to euthanasia, and foal limbs were analysed by quantitative MRI, structural MRI, biomechanical testing and chondrocyte gene expression.

RESULTS

Osteochondral lesions were detected with both radiography and structural MRI in foals from both enrofloxacin-treated and untreated mares. Severe cartilage erosions, synovitis and joint capsular thickening were identified in foals treated with enrofloxacin post-natally. Median cartilage T2 relaxation times differed between joints but did not differ between treatment groups.

MAIN LIMITATIONS

A small sample size was assessed and there was no long-term follow-up.

CONCLUSION

While further research is needed to address long-term foal outcomes, no differences were seen in advanced imaging, biomechanical testing or gene expression by 30 days of age, suggesting that enrofloxacin may be a safe and useful antibiotic for select bacterial infections in pregnant mares.

摘要

背景

最近的研究表明,氟喹诺酮类药物,特别是恩诺沙星及其活性代谢物(环丙沙星),可以穿过马的胎盘,而不会在第一和第三孕期胎儿或新生驹中引起明显的组织学损伤。然而,在子宫内暴露于氟喹诺酮类药物可能会导致标准手段无法检测到的细微损伤;因此,有必要更深入地评估潜在的毒性。

目的

使用定量磁共振成像(qMRI)、生物力学测试和软骨细胞基因表达来评估妊娠晚期暴露于恩诺沙星的驹的四肢。

研究设计

体内和对照终端实验。

方法

在妊娠 280 天的健康母马中分为三组:未治疗组(n=5)、推荐治疗剂量(7.5mg/kg 恩诺沙星,口服,每日 3 次,n=6)或超治疗剂量(15mg/kg,口服,每日 3 次,n=6),连续治疗 14 天。母马足月产仔并哺乳约 30 天。另外 2 只来自未治疗母马的健康驹在产后用恩诺沙星(10mg/kg,口服,每日 3 次,连续 5 天)治疗。在 30 天时,对驹的膝关节、跗关节、肘关节和肩关节进行 X 线摄影,对驹进行安乐死,并通过定量 MRI、结构 MRI、生物力学测试和软骨细胞基因表达分析驹的四肢。

结果

在恩诺沙星治疗和未治疗的母马所产的驹中,都通过 X 线摄影和结构 MRI 检测到了骨软骨病变。在产后用恩诺沙星治疗的驹中,发现了严重的软骨侵蚀、滑膜炎和关节囊增厚。关节的软骨 T2 弛豫时间中位数不同,但治疗组之间无差异。

主要局限性

评估的样本量较小,且没有长期随访。

结论

虽然需要进一步研究来解决驹的长期结局问题,但在 30 天时,在高级成像、生物力学测试或基因表达方面未观察到差异,这表明恩诺沙星可能是一种安全且有用的治疗妊娠母马选择细菌感染的抗生素。

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