Integrative multi-omics profiling reveals an association between lipid metabolism dysregulation and bortezomib-induced cerebral hemorrhage in zebrafish

Abstract

Bortezomib (BTZ), a first-generation proteasome inhibitor, serves as a cornerstone chemotherapeutic agent for Multiple Myeloma (MM), with its clinical application in oncology expanding rapidly in recent years. Using vascular-specific transgenic zebrafish models, we systematically evaluated BTZ-induced toxicity at 4–5 mg/L gradient concentrations and its underlying molecular mechanisms. We found 72-hour BTZ exposure triggered significant intracerebral hemorrhage in zebrafish larvae with concentration-dependent severity, accompanied by cerebrovascular disruption, tight junction gene downregulation, lipid metabolism disorder, ROS accumulation and antioxidant enzyme response, and abnormal nitric oxide activation. This study first reveals that BTZ-induced intracerebral hemorrhage is closely associated with lipid metabolism dysregulation, highlighting lipid disturbance as a potential contributor to cerebrovascular injury.