Beyond hemorrhagic cystitis: unraveling the multifaceted protective roles of sodium 2-mercaptoethanesulfonate

Sodium 2-mercaptoethanesulfonate (MESNA) is widely used as a uroprotective agent to prevent haemorrhagic cystitis (HC) associated with oxazaphosphorine chemotherapy; however, emerging evidence suggests broader cytoprotective potential beyond the urinary system.This review systematically compiles and evaluates preclinical and clinical evidence on the multi-organ protective effects of MESNA, including its roles in mitigating nephrotoxicity, hepatotoxicity, cardiotoxicity, neurotoxicity, pulmonary injury, gastrointestinal damage, and reproductive toxicity.The protective mechanisms of MESNA are primarily attributed to its thiol-mediated detoxification, antioxidant activity, and anti-inflammatory effects, including scavenging of reactive oxygen species (ROS), reduction of lipid peroxidation, modulation of cytokine responses, and maintenance of cellular redox balance.In addition to its established clinical use in oncology, MESNA demonstrates potential applications in surgical procedures, ischemia-reperfusion injury, and combination therapies, although current clinical evidence supporting its systemic protective effects remains limited.Despite its promising therapeutic profile, factors such as short plasma half-life, limited systemic bioavailability, and variability in clinical outcomes highlight the need for further mechanistic studies and well-designed clinical trials to establish its role as a multi-organ cytoprotective agent.