title: Antioxidant and antiapoptotic effects of sea cucumber and valsartan against doxorubicin-induced cardiotoxicity in rats: The role of low dose gamma irradiation.
abstract: Doxorubicin (DOX) is a highly effective antineoplastic drug; however, the clinical use of DOX is limited by its dose dependent cardiotoxicity. This study was conducted to evaluate the cardioprotective effect of sea cucumber and valsartan against DOX-induced cardiotoxicity in rats. Also, the role of exposure to low dose γ radiation (LDR) on each of them was investigated, since LDR could suppress various reactive oxygen species-related diseases. Rats received DOX (2.5mg/kg, ip) in six equal injections over a period of 2weeks, sea cucumber (14.4mg/kg, p.o) and valsartan (30mg/kg, p.o) for 8 successive weeks. Exposure to LDR (0.5Gy) was performed one day prior to DOX. Results revealed that DOX administration elevated serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK-MB) and troponin-I as well as increased cardiac lipid peroxide content and myeloperoxidase (MPO) activity. Additionally, it increased cardiac expressions of iNOS and caspase-3, accompanied by reduction in cardiac total protein and glutathione (GSH) contents. Treatment with sea cucumber or valsartan improved the cardiotoxicity of DOX. Their adjuvant therapy with LDR offers an additional benefit to the cardioprotection of the therapeutic drugs. These results confirmed by histopathological examination. In conclusion, sea cucumber and valsartan alone or combined with LDR attenuated DOX-induced cardiotoxicity via their antioxidant and anti-apoptotic activities and thus might be useful in the treatment of human patients under doxorubicin chemotherapy.
authors.affiliation: Biochemistry Department, Faculty of Science, Ain Shams University, Egypt.
authors.forename: Doaa M
authors.initials: DM
authors.lastname: Ibrahim
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box 29, Nasr City, Cairo, Egypt. Electronic address: rasha_radwan33@yahoo.com.
authors.forename: Rasha R
authors.initials: RR
authors.lastname: Radwan
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box 29, Nasr City, Cairo, Egypt.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Abdel Fattah
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012616:Sea Cucumbers / Q000737:chemistry* / Q000378:metabolism; D019210:Troponin I / Q000097:blood; D000068756:Valsartan / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019210:Troponin I; D004317:Doxorubicin; D000068756:Valsartan; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D053148:Caspase 3; D005978:Glutathione
keywords: Apoptosis; Doxorubicin; Low dose irradiation; Oxidative stress; Sea cucumber; Valsartan