Quasi-LD-Targeted and ONOO--Responsive Fluorescent Probe for Investigating the Interaction of Nonalcoholic Fatty Liver with Drug-Induced Liver Injury.

ABSTRACT

Hepatic lipid droplets (LDs) and peroxynitrite (ONOO-) levels are closely related to nonalcoholic fatty liver disease (NAFLD). Additionally, some drug-induced liver injury (DILI) is often associated with ONOO-. Here, we constructed and screened the quasi-LDs-targeted and ONOO--responsive fluorescent probe MBDP-Py+ to investigate the interaction of NAFLD with DILI. By monitoring the upregulation of the ONOO- levels and the accumulation of LDs, MBDP-Py+ was more sensitive and efficient than tissue staining and serum markers detection in evaluating the early toxicity of NAFLD and diagnosing the anticancer-DILI. More importantly, the sensitive enhancement of fluorescence signals demonstrated that in different stages of NAFLD, the dominant element of liver injury was different in the NAFLD combined with DILI mice models. As the degree of NAFLD deepens, the synergistic effect of the two will lead to more serious liver damage.