Ahmed H Mekkawy, Mohammad Breakeit, Md Khalilur Rahman, Krishna Pillai, Anant Solanki, Fany Octavia, Samina Badar, Javed Akhter, Sarah J Valle, David L Morris
{"title":"Safety of BromAc<sup>®</sup> with Mitomycin C during hyperthermic intraperitoneal chemotherapy (HIPEC): a preclinical study.","authors":"Ahmed H Mekkawy, Mohammad Breakeit, Md Khalilur Rahman, Krishna Pillai, Anant Solanki, Fany Octavia, Samina Badar, Javed Akhter, Sarah J Valle, David L Morris","doi":"10.62347/HQJH9945","DOIUrl":null,"url":null,"abstract":"<p><p>Peritoneal cancer patients are often treated with hyperthermic intraperitoneal chemotherapy (HIPEC). BromAc<sup>®</sup>, 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<sup>®</sup>, Mitomycin C (MMC) or BromAc<sup>®</sup>+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<sup>®</sup>, showed higher weight loss during the first 4 days. Whilst the burst pressure was similar in all groups, the BromAc<sup>®</sup> 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<sup>®</sup> concentration in peritoneal fluids increased over 90 min with a higher increase when given with MMC. BromAc<sup>®</sup> 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<sup>®</sup> with or without MMC was safe during HIPEC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 3","pages":"1213-1223"},"PeriodicalIF":3.6000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982722/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/HQJH9945","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.