Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindopril | ||||
Ain Shams Journal of Forensic Medicine and Clinical Toxicology | ||||
Article 7, Volume 34, Issue 1, January 2020, Page 69-81 PDF (1.97 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/ajfm.2020.68226 | ||||
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Authors | ||||
Takwa Salam1; Wesam El-Bakly1; Ahmed Badawy1; Amany Hasanin 1; Mona Raafat2 | ||||
1Department of Clinical Pharmacology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. | ||||
2Department of Histology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. | ||||
Abstract | ||||
Introduction: Doxorubicin is a highly effective anticancer agent with serious cardiotoxic effects. Hypertension is considered as a major risk factor for doxorubicin cardiotoxicity. It should be noted that about one-third of cancer patients have hypertension, and melatonin can have cardio-protective effects. The present study aimed to further investigate the possible beneficial effects of melatonin co-administration to perindopril against doxorubicin cardiotoxicity in hypertensive rats. Method: Rats were randomly assigned to naïve group and N-Omega-Nitro-L-Arginine Methyl Ester Hydrochloride (L-NAME) hypertensive group. L-NAME group was further subdivided into untreated, doxorubicin, doxorubicin / perindopril, doxorubicin/melatonin and doxorubicin/ perindopril / melatonin subgroups. Cardiac functions, CK-MB, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and cardiac percentage area of collagen fibers were evaluated. Results: Combining melatonin with perindopril to doxorubicin produced significant decreases in left ventricular end diastolic pressure, malondialdehyde, TNF-α, and TGF-β. It resulted in significant increases in left ventricular dP/dtmax and SOD, in addition to apparent improvement in cardiac histopathology with a significant decrease in percentage area of collagen deposition compared to perindopril alone. Conclusion: Co-administration of melatonin to perindopril in hypertensive rats who received doxorubicin alleviated doxorubicin cardiac toxicity more than using perindopril alone. These effects could be explained by the reported antihypertensive, anti-inflammatory, anti-oxidant, and anti-fibrotic effects of melatonin. | ||||
Keywords | ||||
Melatonin; Perindopril; Doxorubicin; L-NAME; cardiotoxicity | ||||
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