Isoniazid (INH)-induced liver injury is a great challenge for
tuberculosis treatment. Existing
biomarkers cannot accurately determine the occurrence of this injury in the early stage. Therefore, developing early specific sensitive
biomarkers of INH-induced liver injury is urgent. A rat model of liver injury was established with gastric infusion of INH or INH plus
rifampicin (RFP). We examined seven potential novel serum
biomarkers, namely,
glutamate dehydrogenase (GLDH),
liver-fatty acid-binding protein (L-FABP), high-mobility group box-1 (
HMGB1),
macrophage colony-stimulating factor receptor (MCSF1R),
osteopontin (OPN), total
cytokeratin 18 (
K18), and
caspase-cleaved
cytokeratin-18 (ccK18), to evaluate their sensitivity and specificity on INH-induced liver injury. With the increase of drug dosage, combining with RFP and prolonging duration of administration, the liver injury was aggravated, showing as decreased weight of the rats, upgraded liver index and oxidative stress level, and histopathological changes of liver becoming marked. But the activity of serum
aminotransferases decreased significantly. The area under the curve (AUC) of receiver-operating characteristic (ROC) curve of OPN, L-FABP,
HMGB1, MCSF1R, and GLDH was 0.88, 0.87, 0.85, 0.71, and 0.70 (≥0.7), respectively, and 95% confidence interval of them did not include 0.5, with statistical significance, indicating their potential abilities to become
biomarkers of INH-induced liver injury. In conclusion, we found traditional
biomarkers ALT and AST were insufficient to discover the INH-induced liver injury accurately and OPN, L-FABP, and
HMGB1 can be promising novel
biomarkers.