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Biomed Pharmacother. 2018 Oct;106:443-453. doi: 10.1016/j.biopha.2018.06.161. Epub 2018 Jul 11.

Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis.

Author information

1
Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, İbrahim Çeçen University of Ağrı, Ağrı, Turkey. Electronic address: mkuzu@agri.edu.tr.
2
Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
3
Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
4
Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, Bingöl, Turkey.
5
Department of Pharmacy Professional Sciences, Faculty of Pharmacy, İbrahim Çeçen University of Ağrı, Ağrı, Turkey.

Abstract

Doxorubicin (DOX) is an effective antineoplastic agent of the anthracycline group. However, as with most anticancer drugs, they cause some toxic effects, including major cardiotoxicity and cognitive impairment. In this study, protective effects of morin against DOX-induced cardiotoxicity and neurotoxicity in rats were investigated. Morin was orally administered to rats at a dose of 50 and 100 mg/kg body weight for 10 days. DOX was administered 40 mg/kg body weight by single dose intraperitoneal injection on the 8th day of the study. Both the levels of glutathione (GSH) and malondialdehyde (MDA) were assessed and enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assessed to determine the protective effect of morin against oxidative stress. To determine the anti-inflammatory effect, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB) were assessed in the heart and brain tissues. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CKMB) activities, which are cardiac function markers, and cardiac troponin-I (cTn-I) levels were also determined. Anti-apoptotic effect was determined by anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein cysteine aspartate specific protease-3 (caspase-3) changes. The regulatory role of morin in signal transduction in the brain tissue was assigned with the determination of amount of acetylcholinesterase (AChE), and its healing effect on the central nervous system was determined with imuinohistochemical detection of glial fibrillar acidic protein (GFAP) level. Histopathological evaluation of heart and brain tissues was performed in all groups.

KEYWORDS:

Apoptosis; Doxorubicin; Inflammation; Morin; Oxidative stress

PMID:
29990832
DOI:
10.1016/j.biopha.2018.06.161
[Indexed for MEDLINE]

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