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

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.