Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindopril
Salam, T., El-Bakly, W., Badawy, A., Hasanin, A., Raafat, M. (2020). Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindopril. EKB Journal Management System, 34(1), 69-81. doi: 10.21608/ajfm.2020.68226
Takwa Salam; Wesam El-Bakly; Ahmed Badawy; Amany Hasanin; Mona Raafat. "Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindopril". EKB Journal Management System, 34, 1, 2020, 69-81. doi: 10.21608/ajfm.2020.68226
Salam, T., El-Bakly, W., Badawy, A., Hasanin, A., Raafat, M. (2020). 'Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindopril', EKB Journal Management System, 34(1), pp. 69-81. doi: 10.21608/ajfm.2020.68226
Salam, T., El-Bakly, W., Badawy, A., Hasanin, A., Raafat, M. Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindopril. EKB Journal Management System, 2020; 34(1): 69-81. doi: 10.21608/ajfm.2020.68226

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  XML 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 Hasaninorcid 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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