Possible nonimmunological toxicological mechanisms of vesnarinone-associated agranulocytosis in HL-60 cells: role of reduced glutathione as cytotoxic defense

In conclusion, we present the first demonstration of the cytotoxic effects and ROS production resulting from the MPO/H2O2/Cl- metabolic reaction of vesnarinone and newly identified the causative metabolite, M2, as the N-chloramine metabolite of M1, which induces cytotoxicity in HL-60 cells. Moreover, a protective role of GSH against the cytotoxicity was revealed. These findings suggest a possible nonimmunological cause of vesnarinone agranulocytosis.PMID:38432956 | DOI:10.2131/jts.49.95

Source: Journal of Toxicological Sciences - March 3, 2024 Category: Toxicology Authors: Toshihisa Koga Yuko Sahara Tadaaki Ohtani Kaneko Yosuke Ken Umehara Source Type: research