Safety of BromAc® with Mitomycin C during hyperthermic intraperitoneal chemotherapy (HIPEC): a preclinical study.

IF 3.6 3区 医学 Q2 ONCOLOGY
American journal of cancer research Pub Date : 2025-03-15 eCollection Date: 2025-01-01 DOI:10.62347/HQJH9945
Ahmed H Mekkawy, Mohammad Breakeit, Md Khalilur Rahman, Krishna Pillai, Anant Solanki, Fany Octavia, Samina Badar, Javed Akhter, Sarah J Valle, David L Morris
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引用次数: 0

Abstract

Peritoneal cancer patients are often treated with hyperthermic intraperitoneal chemotherapy (HIPEC). BromAc®, a mixture of bromelain and acetylcysteine, has demonstrated anticancer properties with chemotherapeutic agents. Although bromelain and acetylcysteine have anti-inflammatory, anti-coagulant and wound healing properties, their effect with Mitomycin C is unknown in HIPEC. Hence, we investigated their safety using a rat model. Sixteen Wistar rats were divided into 4 groups (N=4). Controls received saline, whilst the others received BromAc®, Mitomycin C (MMC) or BromAc®+MMC. Three doses were given at 30-minute intervals. Animal weights were monitored for 7 days before euthanasia. Peritoneal fluid and blood samples were collected for pharmacokinetic analysis. Colon anastomosis healing was evaluated with burst pressure and collagen density assessment. Internal organ histology and coagulation factor X were performed in plasma with an enzyme-linked immune assay. All rats were healthy, with similar weight fluctuation patterns, although the MMC-treated rats, with or without BromAc®, showed higher weight loss during the first 4 days. Whilst the burst pressure was similar in all groups, the BromAc® group showed a slightly higher value. Collagen densities were similar in all groups. The results showed that the histology of vital organs of the treated and controls were similar. BromAc® concentration in peritoneal fluids increased over 90 min with a higher increase when given with MMC. BromAc® or the combination did not affect coagulation Factor X. In conclusion, general well-being, wound healing, organ histology, pharmacokinetics and coagulation factor evaluations indicated that BromAc® with or without MMC was safe during HIPEC.

BromAc®联合丝裂霉素C在高温腹腔化疗(HIPEC)中的安全性:一项临床前研究。
腹膜癌患者通常采用腹腔热化疗(HIPEC)治疗。BromAc®是菠萝蛋白酶和乙酰半胱氨酸的混合物,已被证明与化疗药物具有抗癌特性。虽然菠萝蛋白酶和乙酰半胱氨酸具有抗炎、抗凝血和伤口愈合的特性,但它们与丝裂霉素C在HIPEC中的作用尚不清楚。因此,我们用大鼠模型研究了它们的安全性。16只Wistar大鼠分为4组(N=4)。对照组接受生理盐水治疗,其余组接受BromAc®、丝裂霉素C (MMC)或BromAc®+MMC治疗。每隔30分钟给药三次。在安乐死前7天监测动物体重。收集腹膜液和血液样本进行药代动力学分析。用破裂压力和胶原蛋白密度评估结肠吻合口愈合情况。用酶联免疫法测定血浆内脏器组织学和凝血因子X。所有的大鼠都是健康的,体重波动模式相似,尽管mmc治疗的大鼠,无论是否服用BromAc®,在头4天的体重下降幅度更大。虽然所有组的破裂压力相似,但BromAc®组的破裂压力略高。各组胶原蛋白密度相似。结果表明,治疗组和对照组的重要脏器组织结构相似。腹膜液中BromAc®浓度在90分钟内增加,与MMC给予时增加幅度更高。总之,总体健康状况、伤口愈合、器官组织学、药代动力学和凝血因子评估表明,在HIPEC期间,BromAc®联合或不联合MMC是安全的。
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来源期刊
自引率
3.80%
发文量
263
期刊介绍: The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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