title: Grape seed and skin extract protects against acute chemotherapy toxicity induced by doxorubicin in rat heart.
abstract: Doxorubicin (Dox), an antitumor anthracycline antibiotic, plays a key role in the treatment of many neoplastic diseases. However, its chronic administration induces cardiomyopathy. Increased oxidative stress is a major factor implicated in Dox-induced cardiotoxicity. We hypothesized that a pre-treatment with grape seed and skin extract (GSE), commonly used as an antioxidant agent, may alleviate this cardiotoxicity. Rats were treated with GSE (500 mg/kg bw) by intraperitoneal injection during 8 days. On the 4th day, rats were administered a single dose of Dox (20 mg/kg). At the end of the treatment, their hearts were Langendorff-perfused, subjected to ischemia/reperfusion (I/R) injury, and left ventricular functions as heart rate and developed pressure measured. Hearts were also used to determine free iron, H2O2, Ca2+, lipoperoxidation, carbonylation and antioxidant enzymes such as superoxide dismutase (SOD), catalase and peroxidase. Doxorubicin drastically affected heart activity as evidenced after I/R experiments. This effect was associated with an increase in heart free iron and a decrease in Ca2+ concentrations. This effect may have contributed to oxidative stress as assessed by high lipoperoxidation and carbonylation level. GSE counteracted Dox-induced disturbances of hemodynamic parameters, alleviated oxidative stress as assessed by normalized iron and Ca2+ levels and increased SOD activity especially the Mn isoform.
authors.affiliation: Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis, Campus Universitaire El Manar II, 2092 Tunis, Tunisia. meherzia.mokni@fst.rnu.tn
authors.forename: Meherzia
authors.initials: M
authors.lastname: Mokni
authors.forename: Sonia
authors.initials: S
authors.lastname: Hamlaoui-Guesmi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Amri
authors.forename: Lamjed
authors.initials: L
authors.lastname: Marzouki
authors.forename: Ferid
authors.initials: F
authors.lastname: Limam
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Aouani
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054715:Cardiotoxins / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D027843:Vitis
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002316:Cardiotonic Agents; D054715:Cardiotoxins; D056604:Grape Seed Extract; D004317:Doxorubicin