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亚麻醉剂量氯胺酮作为5-氟尿嘧啶诱导的恶病质模型治疗方法的临床前研究

A Pre-Clinical Study of Sub-Anesthetic Ketamine as Remedy in 5-Fluorouracil-Induced Cachexia Model.

作者信息

Wang James, Lin Zen-Cheng, Weng Brian Bor-Chun

机构信息

Astromedical Biotechnology, LLC, New Taipei City 25147, Taiwan.

Department of Microbiology, Immunology, and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.

出版信息

Life (Basel). 2022 Dec 20;13(1):8. doi: 10.3390/life13010008.

Abstract

Around 0.5-1% of the world population is suffering from cachexia. In particular, cancer patients under cancer radio-chemotherapy have a high prevalence of cachexia, especially during the end stages of therapeutic treatment. Clinically, chemotherapeutic 5-fluorouracil (5-Fu) treatment often leads to the development of adverse effects, such as leukopenia, immune dysfunction, anorexia, muscle wasting, etc., and 5-Fu also tends to exacerbate the occurrence of cancer cachexia. Currently, there are very limited drug choices when seeking to revive cachexia patient's health quality while enduring a full therapeutic regimen as part of advanced cancer therapy. The present study employed chemotherapeutic drug 5-Fu-induced cachexia-like conditions in Balb/c mice. After 8 days of 5-Fu treatment, mice had begun to show cachexia-like symptoms such as weight loss and reduced food intake. After one day of washing out, the cachexia animals received a single dose of either saline solution as a mock dose or a low dose (15 mg/kg BW) or high dose (30 mg/kg BW) of ketamine at day 10. For the following 7 days, food intake, body weight, and mortality were monitored. Data were analyzed with the LOCF (last observation carried forward) method. Improved survival rates were obtained in ketamine groups. Ketamine administration at the high dose of 30 mg/kg BW demonstrated effectively diminished weight loss due to cachexia, and also successfully improved overall survival. The current study demonstrates that a sub-anesthetic level of ketamine administration supports overall beneficial outcomes in 5-Fu-induced cachexia and outlook as a potential clinical remedy.

摘要

全球约0.5%-1%的人口患有恶病质。特别是接受癌症放化疗的癌症患者恶病质患病率很高,尤其是在治疗后期。临床上,化疗药物5-氟尿嘧啶(5-Fu)治疗常导致不良反应的发生,如白细胞减少、免疫功能障碍、厌食、肌肉萎缩等,且5-Fu还往往会加重癌症恶病质的发生。目前,在作为晚期癌症治疗一部分的完整治疗方案中,在寻求恢复恶病质患者健康质量时,药物选择非常有限。本研究在Balb/c小鼠中采用化疗药物5-Fu诱导类似恶病质的状况。5-Fu治疗8天后,小鼠开始出现类似恶病质的症状,如体重减轻和食物摄入量减少。在停药一天后,恶病质动物在第10天接受单剂量生理盐水作为模拟剂量或低剂量(15mg/kg体重)或高剂量(30mg/kg体重)的氯胺酮。在接下来的7天里,监测食物摄入量、体重和死亡率。数据采用末次观察结转(LOCF)法进行分析。氯胺酮组的存活率有所提高。30mg/kg体重的高剂量氯胺酮给药有效减少了恶病质导致的体重减轻,也成功提高了总体存活率。当前研究表明,亚麻醉水平的氯胺酮给药对5-Fu诱导的恶病质具有总体有益效果,有望成为一种潜在的临床治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9844/9866993/7f0b9856530e/life-13-00008-sch001.jpg

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