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调节结肠氧化应激标志物和临床参数:一种在5-氟尿嘧啶方案期间管理副作用的潜在辅助疗法。

Modulated Colonic Oxidative Stress Markers and Clinical Parameters: A Potential Adjuvant Therapy to Manage Side Effects During 5-FU Regimen.

作者信息

Repici Alberto, Capra Anna Paola, Hasan Ahmed, Basilotta Rossella, Scuderi Sarah Adriana, Campolo Michela, Paterniti Irene, Esposito Emanuela, Ardizzone Alessio

机构信息

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.

Center of Neuroscience, School of Advanced Studies, University of Camerino, 62032 Camerino, Italy.

出版信息

Int J Mol Sci. 2024 Dec 3;25(23):12988. doi: 10.3390/ijms252312988.

Abstract

One of the most used chemotherapy agents in clinical practice is 5-Fluorouracil (5-FU), a fluorinated pyrimidine in the category of antimetabolite agents. 5-FU is used to treat a variety of cancers, including colon, breast, pancreatic, and stomach cancers, and its efficacy lies in its direct impact on the patient's DNA and RNA. Specifically, its mechanism blocks the enzymes thymidylate synthetase and uracil phosphatase, inhibiting the synthesis of uracil, which cannot be incorporated into nuclear and cytoplasmic RNA. Despite being one of the most used drugs in oncology, it is associated with several significant side effects, including inflammation of the mouth, loss of appetite, and reduction in blood cells. In our study, we examined the reduction of side effects in a 5-FU regimen administered at doses of 15 mg/kg and 6 mg/kg for 14 days in 6-week-old male Sprague-Dawley rats. On the 14th day, the rats were treated orally for 2 weeks with 100 mg/kg of , a well-known seaweed from the Ulvaceae family, which has demonstrated powerful biological properties. The administration of this green alga alleviated the side effects of 5-FU, improving several parameters including body weight, food intake, and diarrhea index. It also helped reduce side effects in the blood, kidneys, and liver. Histological and molecular analyses were conducted on serum and colon tissues from the rats, examining changes in colon structure and the release of oxidative stress markers such as iNOS, COX-2, and nitrotyrosine. Several biochemical indicators, including SOD, CAT, GSH, MDA, and ascorbic acid, were also evaluated. Overall, our data indicated to be a promising therapeutic against 5-FU's adverse effects, therefore, it could be worthwhile to investigate the possibility of using this alga in safer cancer treatment formulations. Certainly, future preclinical and clinical studies could assess the alga's efficacy in diverse cancer treatment regimens, exploring its role as an adjuvant therapy that may reduce chemotherapy-related toxicity without compromising therapeutic outcomes.

摘要

临床实践中最常用的化疗药物之一是5-氟尿嘧啶(5-FU),它是一种抗代谢药物类别的氟化嘧啶。5-FU用于治疗多种癌症,包括结肠癌、乳腺癌、胰腺癌和胃癌,其疗效在于对患者DNA和RNA的直接影响。具体而言,其作用机制阻断胸苷酸合成酶和尿嘧啶磷酸酶,抑制尿嘧啶的合成,而尿嘧啶无法掺入核RNA和细胞质RNA。尽管它是肿瘤学中最常用的药物之一,但它会引发多种严重副作用,包括口腔炎症、食欲不振和血细胞减少。在我们的研究中,我们在6周龄雄性Sprague-Dawley大鼠中,研究了以15mg/kg和6mg/kg的剂量给药5-FU 14天的方案中副作用的减轻情况。在第14天,给大鼠口服100mg/kg的 ,这是一种来自石莼科的著名海藻,已证明具有强大的生物学特性。这种绿藻的给药减轻了5-FU的副作用,改善了包括体重、食物摄入量和腹泻指数在内的多个参数。它还有助于减轻血液、肾脏和肝脏的副作用。对大鼠的血清和结肠组织进行了组织学和分子分析,检查结肠结构的变化以及氧化应激标志物如诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)和硝基酪氨酸的释放。还评估了包括超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、丙二醛(MDA)和抗坏血酸在内的几种生化指标。总体而言,我们的数据表明 对5-FU的不良反应具有有前景的治疗作用,因此,研究在更安全的癌症治疗配方中使用这种海藻的可能性可能是值得的。当然,未来的临床前和临床研究可以评估这种海藻在不同癌症治疗方案中的疗效,探索其作为辅助治疗的作用,即可能在不影响治疗效果的情况下降低化疗相关毒性。 (注:原文中“On the 14th day, the rats were treated orally for 2 weeks with 100 mg/kg of , a well-known seaweed from the Ulvaceae family”这里“100 mg/kg of ”后面缺失具体物质名称)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e6/11641785/ec039be2646a/ijms-25-12988-g001.jpg

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