Biomarkers associated with binaprofen‑induced liver injury

Drug‑induced liver injury (DILI) is a common hepatic disease. The identification of biomarkers for DILI prediction is critical for rational drug use. The aim of the present study was to investigate liver injury caused by binaprofen and identify proteins that may serve as early biomarkers to predict DILI. For in vivo DILI assays, zebrafish were exposed to acetaminophen (APAP) and binaprofen for 12‑96 h before lethal concentration 50 (LC50), histopathological analysis, conventional and non‑conventional biomarker measurements were conducted. In vitro assays were performed in cultured liver cells; after 6‑24 h treatment with APAP and binaprofen the same measurements were conducted as aforementioned. The in vivo assays indicated that the LC50 of APAP was 5.2 mM, whereas the LC50 of binaprofen was 1.2 mM; 12‑48 h post‑treatment, liver cells exhibited mild to moderate vacuolization in a time‑ and concentration‑dependent manner in response to both drugs. During this time, conventional and non‑conventional biomarkers were also altered in a time‑ and concentration‑dependent manner; however, alterations in the levels of non‑conventional biomarkers occurred at an earlier time point compared with conventional biomarkers. The in vitro assays indicated that the half maximal inhibitory concentration (IC50) of APAP was 16.2 mM, whereas the IC50 of binaprofen was 5.3 mM; 12‑48 h post‑treatment, cultured liver cells exhibited mild to moderate swelling in a time‑ and concentration‑dependent manner. Alterations in the levels of conventional and non‑conventional biomarkers were similar to those observed in the in vivo assays. As a non‑steroidal anti‑inflammatory drug, binaprofen exhibited expected levels of liver toxicity in in vitro and in vivo assays, which were similar to APAP. Total bile acid and argininosuccinate lyase were identified as early biomarkers, which could accurately predict onset of binaprofen‑induced liver injury.