Tag : Toxicity

Tokyo: Cisplatin is commonly used as a chemotherapeutic drug in the treatment of many solid tumours, including bladder, ovarian, and esophageal tumours. However, when it is metabolised by an enzyme called "cysteine conjugate beta-lyase 1 (CCBL1)," it is transformed to "thiol-cisplatin," a highly active poisonous metabolite. Though cisplatin treatment is accompanied with numerous adverse effects, this metabolite is known to induce kidney damage and is thus a key dose-limiting side effect of cisplatin treatment. This research was headed by Associate Professor Hidetsugu Fujigaki of Fujita Health University and will be published in the journal Molecular Cancer Therapeutics on May 10, 2023. As a treatment, vigorous or intravenous short-term injection of saline and mannitol is regarded standard of care. However, in many situations, these hydration regimes need hospitalisation. To enhance patient care, a group of Japanese researchers discovered that inhibiting the CCBL1-mediated metabolism of cisplatin with the aromatic ketone 2',4',6'-trihydroxyacetophenone (THA) can minimise cisplatin toxicity without compromising the drug's effectiveness] Speaking about the study, Associate Professor Hidetsugu Fujigaki and a co-author, Nao Sukeda, a Master's student from Fujita Health University's Graduate School of Health Sciences say, "Using a high-throughput screening assay, we identified THA as an inhibitor of CCBL1. THA inhibited human CCBL1 b-elimination activity in a concentration-dependent manner." To this end, the researchers first screened compound libraries for possible inhibitors of CCBL1, the enzyme responsible for the synthesis of cisplatin's toxic metabolite. This screening yielded THA, a naturally occurring compound from the Curcuma comosa ...