title: Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity.
abstract: The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and -dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post- but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, -dP/dtmax, and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dtmax. Therefore, we conclude that concurrent or post- but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.
authors.affiliation: a Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Hussein F
authors.initials: HF
authors.lastname: Sakr
authors.affiliation: a Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Amr M
authors.initials: AM
authors.lastname: Abbas
authors.affiliation: b Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Ayman Z
authors.initials: AZ
authors.lastname: Elsamanoudy
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D054715:Cardiotoxins / Q000633:toxicity*; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D004317:Doxorubicin / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D004317:Doxorubicin; D000068756:Valsartan
keywords: apoptose; apoptosis; doxorubicin; doxorubicine; oxidative stress; senescence; stress oxydatif; valsartan