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dc.contributor.authorApiwan Arinnoen_US
dc.contributor.authorChayodom Maneechoteen_US
dc.contributor.authorThawatchai Khuanjingen_US
dc.contributor.authorBenjamin Ongnoken_US
dc.contributor.authorNanthip Prathumsapen_US
dc.contributor.authorTitikorn Chunchaien_US
dc.contributor.authorBusarin Arunsaken_US
dc.contributor.authorSasiwan Kerdphooen_US
dc.contributor.authorKrekwit Shinlapawittayatornen_US
dc.contributor.authorSiriporn C. Chattipakornen_US
dc.contributor.authorNipon Chattipakornen_US
dc.description.abstractDoxorubicin (Dox) is widely used in chemotherapy regimens for several malignant conditions. Unfortunately, cumulative and irreversible cardiotoxicity of Dox is the most prominent adverse effect which limits its use. Several pharmacological interventions which exert antioxidant properties, including melatonin and metformin, have demonstrated beneficial effects against various cardiac pathological conditions. However, the exact molecular mechanisms underlying their cardioprotective effects are not completely understood. We hypothesized that treatment with either melatonin or metformin provides cardioprotection against Dox-induced cardiotoxicity through mitochondrial protection. Thirty-two male Wistar rats received 6 doses of either 0.9% normal saline solution (0.9% NSS, n = 8) or Dox (3 mg/kg, i.p., n = 24). The Dox-treated rats (n = 8/group) were co-treated with: 1) Vehicle (0.9% NSS), 2) Melatonin (10 mg/kg/day), and 3) Metformin (250 mg/kg/day) for 30 consecutive days via oral gavage. Following the treatment, left ventricular (LV) function, oxidative stress, inflammation, mitochondrial function, dynamics, biogenesis and bioenergetics, mitophagy, autophagy, and apoptosis were determined. Dox induced excessive oxidative stress, inflammation, autophagy, apoptosis, reduced mitochondrial function, dynamics balance, biogenesis, and bioenergetics leading to LV dysfunction. Treatment with either melatonin or metformin exerted equal measures of cardioprotection via reducing oxidative stress, inflammation, autophagy, apoptosis, and improved mitochondrial function, dynamics balance, biogenesis, and bioenergetics in the Dox-treated rats. Melatonin and metformin exerted both anti-cancer and cardioprotective properties, suggesting they have potential roles in concomitant therapy in cancer patients receiving Dox treatment.en_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleCardioprotective effects of melatonin and metformin against doxorubicin-induced cardiotoxicity in rats are through preserving mitochondrial function and dynamicsen_US
article.title.sourcetitleBiochemical Pharmacologyen_US
article.volume192en_US of Medicine, Chiang Mai Universityen_US Mai Universityen_US
Appears in Collections:CMUL: Journal Articles

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