Tabassum Heena, Waseem Mohammad, Parvez Suhel, Qureshi M Irfan
Proteomics and Bioinformatics Laboratory, Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Arch Med Res. 2015 Nov;46(8):597-603. doi: 10.1016/j.arcmed.2015.10.002. Epub 2015 Nov 10.
Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions.
The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin.
Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed.
Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation.
奥沙利铂是一种广泛应用的铂类化疗药物,常用于治疗结直肠癌。不幸的是,这种重要药物的疗效因严重副作用而受到影响,如神经病变、耳毒性、胃肠道毒性和血液学毒性。最近,也有少数研究表明奥沙利铂治疗的患者会出现肝毒性。线粒体已成为各种毒性(包括可导致肿瘤性疾病的肝毒性)中抗癌药物的作用靶点。氧化应激是线粒体毒性的一个公认生物标志物。本研究的目的是在体外条件下研究奥沙利铂对分离的肝线粒体造成的剂量依赖性损伤。
本研究在从Wistar大鼠肝脏分离的线粒体中进行。在体外条件下,将奥沙利铂与线粒体以剂量依赖性方式孵育。评估氧化应激指标、非酶和酶抗氧化剂,观察对抗奥沙利铂诱导毒性的整体手段。
奥沙利铂导致线粒体氧化应激指标脂质过氧化和蛋白质羰基显著升高。还观察到非酶抗氧化剂水平和酶抗氧化剂活性的改变。
氧化应激在奥沙利铂的线粒体毒性中起重要作用。活性氧介导的脂质过氧化和蛋白质羰基形成损害了肝组织的完整性。