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Trimetazidine improved adriamycin‐induced cardiomyopathy by downregulating TNF ‐α, BAX , and VEGF immunoexpression via an antioxidant mechanism
Author(s) -
Eid Basma G.,
ElShitany Nagla Abd ElAziz,
Neamatallah Thikryat
Publication year - 2021
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.23120
Subject(s) - cardiotoxicity , pharmacology , superoxide dismutase , malondialdehyde , trimetazidine , glutathione peroxidase , glutathione , chemistry , tumor necrosis factor alpha , catalase , antioxidant , oxidative stress , vascular endothelial growth factor , medicine , toxicity , biochemistry , enzyme , vegf receptors
Few studies have reported a prophylactic effect of the anti‐ischemic trimetazidine (TRI) against cardiac toxicity caused by adriamycin (ADR). However, the mechanism of action of TRI remained incomplete. The cardioprotective mechanism(s) of TRI against ADR‐induced cardiotoxicity was investigated in this study. Cardiotoxicity was induced in three groups of Wistar rats by injecting a single dose of ADR (10 mg/kg, i.p.). TRI was administered in two doses regimen, low (L) (2.5 mg/kg, i.p.) and high (H) (10 mg/kg, i.p.). The results of the study showed that both TRI L and H doses improved cardiac enzymes and pathology, while only the TRI H dose improved the electrocardiogram. Both TRI L and H doses decreased malondialdehyde and increased reduced glutathione and superoxide dismutase. Only TRI H dose increased glutathione peroxidase and catalase. Both TRI L and H doses decreased interleukin‐1 beta and tumor necrosis factor‐alpha (TNF‐α). Both TRI L and H doses downregulated TNF‐α, BAX, and vascular endothelial growth factor cardiac protein expression. The data obtained in this study provided evidence that TRI opposed ADR‐induced cardiotoxicity. The mechanism could be due to improved antioxidant levels as well as inhibition of inflammation and programmed cell death.