title: Efficacy of grape seed and skin extract against doxorubicin-induced oxidative stress in rat liver.
abstract: Doxorubicin (Dox) is an anthracycline used in chemotherapy, although it causes toxicity and oxidative stress. Grape seed and skin extract (GSSE) is a mixture of polyphenolic compounds with antioxidant properties. To evaluate the hepato-toxicity of Dox on healthy rats as well as the protective effect of GSSE, rats were treated with GSSE (500mg/kg bw) during 8 days. At the 4th day of treatment, they received a single dose of Dox (20 mg/kg bw). After the treatment (9th day), livers were collected and processed for oxidative stress status. Dox increased MDA (+ 900%), decreased catalase (-60%) and increased peroxidase (+90%) and superoxide dismutase (+100%) activities. In this latter case Dox mainly increased the iron isoform. Furthermore Dox altered intracellular mediators as catalytic free iron (-75%), H₂O₂(-75%) and calcium (+30%). Dox also affected liver function by elevating plasma triacylglycerol and transaminases and liver morphology by altering its typical architecture. Importantly all Dox-induced liver disturbances were alleviated upon GSSE treatment. Dox induced liver toxicity and an oxidative stress mainly characterized by increased lipoperoxidation but not protein carbonylation. GSSE efficiently protected the liver from Dox-induced toxicity and appeared as a safe adjuvant that could be incorporated into chemotherapy protocols.
authors.affiliation: Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar Tunis, Tunisie.
authors.forename: Meherzia
authors.initials: M
authors.lastname: Mokni
authors.affiliation: Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar Tunis, Tunisie.
authors.forename: Sonia
authors.initials: S
authors.lastname: Hamlaoui
authors.affiliation: Laboratoire des Substances Bioactives, Centre de Biotechnologie, Technopole Borj-Cedria, Hammam-Lif, Tunisie.
authors.forename: Safouen
authors.initials: S
authors.lastname: Kadri
authors.affiliation: Laboratoire des Substances Bioactives, Centre de Biotechnologie, Technopole Borj-Cedria, Hammam-Lif, Tunisie.
authors.forename: Ferid
authors.initials: F
authors.lastname: Limam
authors.affiliation: Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar Tunis, Tunisie.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Amri
authors.affiliation: Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar Tunis, Tunisie.
authors.forename: Lamjed
authors.initials: L
authors.lastname: Marzouki
authors.affiliation: Laboratoire des Substances Bioactives, Centre de Biotechnologie, Technopole Borj-Cedria, Hammam-Lif, Tunisie.
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Aouani
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005638:Fruit; D056604:Grape Seed Extract / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010946:Plants, Medicinal; D017208:Rats, Wistar; D012639:Seeds; D013997:Time Factors; D027843:Vitis / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D015415:Biomarkers; D056604:Grape Seed Extract; D004317:Doxorubicin; D007501:Iron; D002118:Calcium