title: Protective role of naringenin against doxorubicin-induced cardiotoxicity in a rat model: histopathology and mRNA expression profile studies.
abstract: Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic agents. Its efficacy has been proven in various malignancies alone and combined with other cytocidal agents. However, the clinical usefulness of DOX is restricted by the risk of developing congestive heart failure. Formation of free radicals and oxidative stress during DOX treatment may result in adverse side effects. Naringenin (NAR) is one of the potential bioflavonoids with excellent antioxidant properties and free-radical scavenging capability. This study was designed to evaluate whether NAR exerts a protective role against DOX-induced cardiotoxicity in rats. Male Wistar rats were administered DOX (3 mg/kg) intravenously for 10 consecutive weeks along with oral treatment with NAR (50 mg/kg/day). DOX-induced cardiac toxicity was characterized by the marked biochemical alterations of lactic acid dehydrogenase (LDH), troponin T, malondialdehyde (MDA), reduced cardiac enzymatic activities (SOD, GPx, CAT) and histopathological observations. Administration of NAR to DOX-challenged rats ameliorated alterations in biochemical markers. Indeed, DOX increased the mRNA expression levels of TGF-β1, TNF-α, IL-6, and IL-10 compared with the control group. However, cotreatment with NAR attenuated the mRNA expression levels of these inflammatory markers and improved histological cardiac damage and cardiac functions. Thus, supplementation of NAR may be beneficial in reducing DOX toxicity.
authors.affiliation: School of Biological Sciences, Madurai Kamaraj University, Madurai- 625 021, India.
authors.forename: Swathika
authors.initials: S
authors.lastname: Subburaman
authors.affiliation: School of Biological Sciences, Madurai Kamaraj University, Madurai- 625 021, India.
authors.forename: Kumaresan
authors.initials: K
authors.lastname: Ganesan
authors.affiliation: School of Biological Sciences, Madurai Kamaraj University, Madurai- 625 021; Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Chennai-603 103, India.
authors.forename: Murugesan
authors.initials: M
authors.lastname: Ramachandran
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D044950:Flavanones; D012333:RNA, Messenger; D004317:Doxorubicin; C005273:naringenin