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Molecular biomarkers of cantharidin‐induced cardiotoxicity in Sprague‐Dawley rats: Troponin T, vascular endothelial growth factor and hypoxia inducible factor‐1α
Author(s) -
Youyou Zhang,
Yalei Yu,
Jie Zhang,
Chuhuai Guan,
Liang Liu,
Liang Ren
Publication year - 2020
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3974
Subject(s) - cantharidin , vascular endothelial growth factor , troponin complex , h&e stain , medicine , endocrinology , troponin , immunohistochemistry , myocardial infarction , biology , vegf receptors , ecology
Abstract Early diagnosis of cantharidin‐induced myocardial injury is the key to reduce the fatality rate in clinical practice. The purpose of the present study was to explore biomarkers that can be used for the prediction and diagnosis of cantharidin‐induced myocardial injury. Of 65 male Sprague‐Dawley rats weighing 200‐230 g, 25 rats were divided into five groups according to the administration dose of cantharidin (0, 1.34, 2.67, 4 and 5.34 mg/kg; n = 5 per group) and the other 40 rats were treated with 2.67 mg/kg cantharidin and divided into nine groups according to the administration time (0, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours; n = 4 per group). Pathological changes of hypoxia, necrosis and inflammation were confirmed in heart samples that were exposed to cantharidin by hematoxylin‐eosin staining and overall scores of pathological changes among heart samples in cantharidin exposure groups showed an increasing trend compared with in the control group. Coexpression of vascular endothelial growth factor (VEGF), hypoxia inducible factor‐1α (HIF‐1α) and caspase9 was shown in the myocardium by immunofluorescence staining. Western blotting results showed that expression of VEGF, HIF‐1α and caspase9 in cantharidin‐treated rat hearts showed an increasing trend compared with in the control group. Results of enzyme‐linked immunosorbent assay suggested that plasma levels of troponin T (TN‐T), VEGF and HIF‐1α were elevated at different intervals after cantharidin administration, and VEGF and HIF‐1α had a significant linear relationship with TN‐T that was verified by multiple linear regression analysis. Preliminary results serve to illustrate that TN‐T, VEGF and HIF‐1α might be valuable molecular markers in cantharidin‐induced myocardial injury and that diagnostic accuracy needs to be studied further.