Serum biomarkers of isoniazid-induced liver injury: Aminotransferases are insufficient, and OPN, L-FABP and HMGB1 can be promising novel biomarkers
| Autor: | Qi-Zhi Zhang, Yun Li, Wen-Wen Luo, Xuan Cheng, Jia-Lian Zhu, Huai-rong Xiang, Wen-Xing Peng |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Antitubercular Agents Toxicology medicine.disease_cause Fatty Acid-Binding Proteins Gastroenterology Rats Sprague-Dawley Cytokeratin Internal medicine medicine Isoniazid Animals Osteopontin HMGB1 Protein Transaminases Liver injury biology business.industry Glutamate dehydrogenase Area under the curve medicine.disease Rats biology.protein Chemical and Drug Induced Liver Injury business Oxidative stress Rifampicin medicine.drug |
| Zdroj: | Journal of applied toxicology : JATREFERENCES. 42(3) |
| ISSN: | 1099-1263 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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