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Single‐Cell Proteomic Profiling of Hepatocytes Reveals Heterogeneous Responses to Hepatotoxic Drugs Nevirapine, Efavirenz, and Acetaminophen

Drug‐induced hepatotoxicity remains a leading cause of the withdrawal of drugs from the global market. Changes in the proteomic profile of hepatocytes following exposure to known hepatotoxic drugs could provide insight into the mechanisms underlying drug‐induced hepatotoxicity. Thus, we aimed to employ mass spectrometry (MS)‐based proteomics to investigate the impact of a subset of known hepatotoxic drugs, namely, efavirenz (EFV), nevirapine (NVP), and acetaminophen (APAP) on the human hepatocyte proteome in vitro. In addition, to add further granularity to the analysis and to understand potential cell‐to‐cell variability in the proteomic response to the above‐mentioned drugs, single‐cell proteomics was employed.