Effects of Melatonin and Adrenomedullin in Reducing the Cardiotoxic Effects of Doxorubicin in Rats

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dc.contributor.authorDurdagi G.
dc.contributor.authorPehlivan D.Y.
dc.contributor.authorOyar E.O.
dc.contributor.authorBahceci S.A.
dc.contributor.authorOzbek M.
dc.date.accessioned2024-07-22T08:05:57Z
dc.date.available2024-07-22T08:05:57Z
dc.date.issued2021
dc.description.abstractThe main disadvantage of doxorubicin (DOX) is that it has cardiotoxic side effects. Our aim is to evaluate the cardioprotective effects of adrenomedullin (ADM) and to compare these effects with melatonin (MEL), it’s cardioprotective effects are well known. Rats were divided into four groups: Control group (0.9% NaCl solution, intravenously), Doxorubicin group (45 mg/kg DOX, intravenously), Doxorubicin + Melatonin group (DOX + MEL, 10 mg/kg melatonin, intraperitoneally), Doxorubicin + Adrenomedullin group (DOX + ADM, 12 µg/kg adrenomedullin, intraperitoneally). A single dose of DOX was injected to the experimental groups on day 5, and a single dose of 0.9% NaCl solution was injected to the control group through the tail vein. The animals were anesthetized and ECG recordings were obtained on day 8. For the purpose of biochemical and histological analysis, cardiac tissue biopsy was obtained after ECG recordings. Compared to the control group, the DOX group had significantly increased duration of QRS complex, PR interval, QT interval and QTc interval. QRS complex, QT interval and QTc interval were prolonged with the administration of DOX and shortened with the administration of ADM. MEL weakened the toxic effects of DOX on the cardiac tissue and it is shown histologically. DOX increased interleukins (IL-1α, IL-6, IL-18), tumor necrosis factor-α (TNF-α), hypoxia-inducible factor 1-alpha (HIF-1α), malondialdehyde (MDA), nitric oxide (NO), creatine kinase myocardial band (CK-MB), and total oxidant status (TOS) levels in cardiac tissue, while reducing total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CAT) levels. MEL administration decreased the levels of CK-MB, MDA, IL-1α, IL-6, IL-18, NO, and TNF-α, whereas ADM only decreased IL-1α, IL-18, MDA and TNF-α levels. In summary, these results show that DOX has toxic effects on rat cardiac tissue which is documented histologically, electrocardiographically and biochemically. MEL alleviated histological damage and showed improvement on the several biochemical parameters of cardiac tissue. ADM brought several electrocardiographic and biochemical parameters closer to normal values. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
dc.identifier.DOI-ID10.1007/s12012-020-09625-y
dc.identifier.issn15307905
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13316
dc.language.isoEnglish
dc.publisherSpringer
dc.subjectAction Potentials
dc.subjectAdrenomedullin
dc.subjectAnimals
dc.subjectAnti-Inflammatory Agents
dc.subjectAntioxidants
dc.subjectCardiotoxicity
dc.subjectCytokines
dc.subjectDisease Models, Animal
dc.subjectDoxorubicin
dc.subjectHeart Diseases
dc.subjectHeart Rate
dc.subjectHypoxia-Inducible Factor 1, alpha Subunit
dc.subjectInflammation Mediators
dc.subjectMale
dc.subjectMelatonin
dc.subjectMyocytes, Cardiac
dc.subjectNitric Oxide
dc.subjectOxidative Stress
dc.subjectRats, Wistar
dc.subjectadrenomedullin
dc.subjectcatalase
dc.subjectcreatine kinase MB
dc.subjectdoxorubicin
dc.subjecthypoxia inducible factor 1alpha
dc.subjectinterleukin 18
dc.subjectinterleukin 6
dc.subjectmalonaldehyde
dc.subjectmelatonin
dc.subjectnitric oxide
dc.subjectsuperoxide dismutase
dc.subjecttumor necrosis factor
dc.subjectadrenomedullin
dc.subjectantiinflammatory agent
dc.subjectantioxidant
dc.subjectautacoid
dc.subjectcytokine
dc.subjectdoxorubicin
dc.subjectHif1a protein, rat
dc.subjecthypoxia inducible factor 1alpha
dc.subjectmelatonin
dc.subjectnitric oxide
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectArticle
dc.subjectcardiotoxicity
dc.subjectcomparative effectiveness
dc.subjectcontrolled study
dc.subjectheart protection
dc.subjectmale
dc.subjectnonhuman
dc.subjectPR interval
dc.subjectpriority journal
dc.subjectQRS complex
dc.subjectQTc interval
dc.subjectrat
dc.subjectaction potential
dc.subjectanimal
dc.subjectcardiac muscle cell
dc.subjectcardiotoxicity
dc.subjectcomparative study
dc.subjectdisease model
dc.subjectdrug effect
dc.subjectheart disease
dc.subjectheart rate
dc.subjectmetabolism
dc.subjectoxidative stress
dc.subjectpathology
dc.subjectpathophysiology
dc.subjectWistar rat
dc.titleEffects of Melatonin and Adrenomedullin in Reducing the Cardiotoxic Effects of Doxorubicin in Rats
dc.typeArticle

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