Evaluation of biomarkers for doxorubicin‑induced cardiac injury in rats

Abstract

Drug-induced cardiotoxicity is a leading cause of failure in drug development and predicting its occurrence in non-clinical studies is the primary preventive measure. The present study aimed to evaluate the changes in biomarkers during acute and chronic myocardial injury induced by doxorubicin (DOX) in rats. A rat model of acute myocardial injury was established through a single-dose, intraperitoneal injection of DOX (40 mg/kg), the changes in biomarkers were measured at 2, 4, 8 and 24 h after administration, following DOX administration, creatine kinase (CK) and fatty acid-binding protein 3 (FABP3) levels increased between 8 and 24 h, whereas cardiac troponin I (cTnI) peaked at 8 h. To establish a chronic myocardial injury model, rats received 1, 2 or 3 mg/kg DOX weekly by caudal vein injection for 2, 4, 6 or 7 weeks, the changes in biomarkers were detected at 2, 4, 6 and 8 weeks, the results showed that cTnI increased significantly after 2 and 8 weeks of administration. A significant increase in FABP3 and microRNA (miR)-146b levels was observed after 8 weeks of administration. Receiver operating characteristic curve and correlation analysis showed that cTnI and miR-146b had relatively high predictive values for chronic myocardial injury (area under the curve, 0.83 and 0.71, respectively) and were closely correlated with myocardial damage. These data suggested that CK, cTnI and FABP3 were relatively sensitive to DOX-induced acute myocardial injury, whereas cTnI and miR-146b were relatively sensitive to DOX-induced chronic myocardial injury.

Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats

“…Change in troponin levels is a characteristic marker for cardiac damage and its rise in serum is widely used in clinical practice to diagnose cardiac injury. Previous studies have shown that troponin T was reduced in cardiac tissue, probably because it was released into the circulation after myocardial damage [ 59 , 60 , 61 , 62 , 63 ].…”

Evaluating the Acute Toxicity and In vivo Protective Effect of Standardized Andrographis paniculata Extract against Doxorubicin-induced Cardiotoxicity in Sprague-dawley Rats

“…DOX administration significantly increased cTnI (p < 0.05) which was consistent with the other studies. 44,45 Interestingly, co-treatment with AP extract drastically reduced cTnI level (p < 0.05) (Figure 4). BNP belongs to a group of naturally occurring peptides known as natriuretic peptides (NPs).…”

“…This release of troponins into the blood allows for their detection and measurement in a blood test, serving as a valuable indicator of heart damage. 44 In this study, the level of cTnI was measured in serum. DOX administration significantly increased cTnI (p < 0.05) which was consistent with the other studies.…”