Mokni Meherzia, Hamlaoui Sonia, Kadri Safouen, Limam Ferid, Amri Mohamed, Marzouki Lamjed, Aouani Ezzedine
Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de Tunis. Campus Universitaire El Manar Tunis, Tunisie.
Laboratoire des Substances Bioactives, Centre de Biotechnologie, Technopole Borj-Cedria, Hammam-Lif, Tunisie.
Pak J Pharm Sci. 2015 Nov;28(6):1971-8.
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.
阿霉素（Dox）是一种用于化疗的蒽环类药物，尽管它会引起毒性和氧化应激。葡萄籽和葡萄皮提取物（GSSE）是一种具有抗氧化特性的多酚类化合物混合物。为了评估阿霉素对健康大鼠的肝毒性以及GSSE的保护作用，大鼠在8天内接受GSSE（500mg/kg体重）治疗。在治疗的第4天，它们接受单剂量的阿霉素（20mg/kg体重）。治疗后（第9天），收集肝脏并对其氧化应激状态进行处理。阿霉素使丙二醛增加（+900%），过氧化氢酶减少（-60%），过氧化物酶增加（+90%），超氧化物歧化酶增加（+100%）。在后一种情况下，阿霉素主要增加了铁同工型。此外，阿霉素改变了细胞内介质，如催化性游离铁（-75%）、过氧化氢（-75%）和钙（+30%）。阿霉素还通过升高血浆三酰甘油和转氨酶影响肝功能，并通过改变肝脏的典型结构影响肝脏形态。重要的是，GSSE治疗可减轻所有阿霉素诱导的肝脏紊乱。阿霉素诱导肝脏毒性和氧化应激，其主要特征是脂质过氧化增加而非蛋白质羰基化增加。GSSE有效地保护肝脏免受阿霉素诱导的毒性，并且似乎是一种可纳入化疗方案的安全佐剂。
