Mekkawy Ahmed H, Breakeit Mohammad, Rahman Md Khalilur, Pillai Krishna, Solanki Anant, Octavia Fany, Badar Samina, Akhter Javed, Valle Sarah J, Morris David L
Mucpharm Pty Ltd. Sydney, NSW 2217, Australia.
Department of Surgery, St George Hospital Sydney, NSW 2217, Australia.
Am J Cancer Res. 2025 Mar 15;15(3):1213-1223. doi: 10.62347/HQJH9945. eCollection 2025.
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.
腹膜癌患者通常采用腹腔内热化疗（HIPEC）进行治疗。菠萝蛋白酶与乙酰半胱氨酸的混合物BromAc已显示出与化疗药物联合使用时具有抗癌特性。尽管菠萝蛋白酶和乙酰半胱氨酸具有抗炎、抗凝和促进伤口愈合的特性，但它们与丝裂霉素C在HIPEC中的联合效果尚不清楚。因此，我们使用大鼠模型研究了它们的安全性。16只Wistar大鼠被分为4组（每组n = 4）。对照组接受生理盐水，其他组分别接受BromAc、丝裂霉素C（MMC）或BromAc + MMC。每隔30分钟给予三种剂量。在安乐死之前监测动物体重7天。收集腹腔液和血液样本进行药代动力学分析。通过爆破压力和胶原蛋白密度评估来评价结肠吻合口愈合情况。采用酶联免疫分析法检测血浆中的内脏器官组织学和凝血因子X。所有大鼠均健康，体重波动模式相似，尽管接受MMC治疗的大鼠，无论是否使用BromAc，在最初4天内体重下降幅度更大。虽然所有组的爆破压力相似，但BromAc组的值略高。所有组的胶原蛋白密度相似。结果表明，治疗组和对照组重要器官的组织学相似。腹腔液中BromAc浓度在90分钟内升高，与MMC联合使用时升高幅度更大。BromAc或其组合不影响凝血因子X。总之，一般健康状况、伤口愈合、器官组织学、药代动力学和凝血因子评估表明，无论有无MMC，BromAc在HIPEC期间都是安全的。
