大剂量美洛昔康和卡洛芬对雌性CD1小鼠的毒性作用。

IF 1.2 3区 农林科学 Q3 VETERINARY SCIENCES Journal of the American Association for Laboratory Animal Science Pub Date : 2022-01-01 Epub Date: 2021-12-17 DOI:10.30802/AALAS-JAALAS-21-000071
Lon V Kendall, Alexandrea L Bailey, Benjamin Singh, Whitney McGee
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引用次数: 3

摘要

非甾体类抗炎药美洛昔康和卡洛芬是常用的小鼠镇痛药。目前推荐的美洛昔康剂量为0.2-1.0 mg/kg每日一次,卡洛芬剂量为5-10 mg/kg每日两次,可能不足以在小鼠中提供镇痛作用。几项研究表明,需要高达20毫克/公斤的剂量的美洛昔康和卡洛芬来提供镇痛效果。本研究通过评估高剂量美洛昔康和卡洛芬对肾脏和胃肠道的潜在毒性,调查了它们的临床安全性。雌性CD-1小鼠每天皮下注射20 mg/kg美洛西康、卡洛芬或等量生理盐水,持续3或7 d。第4天,治疗3 d的小鼠安乐死,第8和15天,治疗7 d的小鼠安乐死。采用穿刺取血进行血清化学分析。取结肠粪便进行粪便潜血检查,取组织进行组织病理学检查。与生理盐水对照组相比,药物治疗小鼠在任何时间点的血清化学谱均未发现临床显著变化。在第4天和第8天对小鼠进行评估时,粪便隐血和胃炎的组织学证据与美洛昔康给药有关。到第15天,美洛昔康治疗与粪便隐血或胃炎的存在没有关联。无论治疗时间如何,卡洛芬或盐处理小鼠的粪便隐血与胃炎之间没有关联。这些结果表明,20 mg/kg的美洛昔康给药3或7 d后会引起小鼠胃毒性,应谨慎使用;然而,就所测参数而言,卡洛芬在20毫克/公斤时似乎毒性作用最小。
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Toxic Effects of High-dose Meloxicam and Carprofen on Female CD1 Mice.

The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.

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来源期刊
CiteScore
3.10
自引率
35.30%
发文量
122
审稿时长
6-12 weeks
期刊介绍: The Journal of the American Association for Laboratory Animal Science (JAALAS) serves as an official communication vehicle for the American Association for Laboratory Animal Science (AALAS). The journal includes a section of refereed articles and a section of AALAS association news. All signed articles, including refereed articles and book reviews, editorials, committee reports, and news and commentary, reflect the individual views of the authors and are not official views of AALAS. The mission of the refereed section of the journal is to disseminate high-quality, peer-reviewed information on animal biology, technology, facility operations, management, and compliance as relevant to the AALAS membership. JAALAS accepts research reports (data-based) or scholarly reports (literature-based), with the caveat that all articles, including solicited manuscripts, must include appropriate references and must undergo peer review.
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