Elucidation of the mechanisms of renal toxicity caused by antibacterial cephems

Abstract

Antibacterial cephems are safe drugs used to control various infectious diseases. Meanwhile, cephems cause rare but serious side effects, such as acute tubular necrosis (ATN), due to the cytotoxicity of cephems. However, toxic mechanisms of cephems remain unknown. In this study, we performed comprehensive analysis of the toxic mechanisms, and found that the nuclear accumulation of the ubiquitinated protein-containing aggresomes, called aggresome-like induced structures (ALIS), driven by reactive oxygen species (ROS) is a common feature of cytotoxic cephems, which promotes cephem-induced cytotoxicity.