Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Department of Biochemistry, Jamia Hamdard (Hamdard University), New Delhi, India.
Arch Med Res. 2017 Jan;48(1):55-63. doi: 10.1016/j.arcmed.2017.01.010.
To explore hepatoprotective action of curcumin (CMN, a bioflavonoid) on oxaliplatin (Oxa)-triggered mitochondrial oxidative stress and respiratory chain complexes in liver of rats. Oxa is a ubiquitously utilized platinum-based chemotherapeutic agent commonly used for the treatment of colorectal cancer. Mitochondria have recently emerged as targets for anticancer drugs in several kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. There is a dearth of evidence involving the role of mitochondria in mediating Oxa-evoked hepatotoxicity and its underlying mechanism is still debatable.
The study was performed in mitochondria isolated from liver of Wistar rats. Oxa (200 μg/mL) and CMN (5 μmol) were incubated under in vitro conditions.
Oxa evoked a significant increase in the membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, decrease in reduced glutathione (GSH) and nonprotein thiol (NP-SH) levels. Oxa also caused a marked decline in the activities of enzymatic antioxidants and respiratory chain enzymes (I, II, III and V) in liver mitochondria. CMN pre-treatment significantly prevented the activities of enzymatic antioxidants and mitochondrial respiratory chain enzymes. CMN also restored the LPO and PC contents, GSH and NP-SH levels in liver mitochondria.
CMN intake might be effective in regulation of Oxa-evoked mitotoxicity during chemotherapy. Moreover, it is included in the armamentarium for anticancer agent-induced oxidative stress.
探索姜黄素（CMN，一种生物类黄酮）对奥沙利铂（Oxa）引发的大鼠肝脏线粒体氧化应激和呼吸链复合物的肝保护作用。奥沙利铂是一种广泛使用的铂类化疗药物，常用于治疗结直肠癌。线粒体最近成为多种毒性包括肝毒性的抗癌药物的靶点，肝毒性可导致肿瘤疾病。涉及线粒体在介导奥沙利铂诱发的肝毒性及其潜在机制的证据不足。
本研究在 Wistar 大鼠肝脏分离的线粒体中进行。奥沙利铂（200μg/mL）和 CMN（5μmol）在体外条件下孵育。
奥沙利铂引起膜脂质过氧化（LPO）水平、蛋白质羰基（PC）含量显著增加，还原型谷胱甘肽（GSH）和非蛋白巯基（NP-SH）水平降低。奥沙利铂还导致肝线粒体中酶抗氧化剂和呼吸链酶（I、II、III 和 V）的活性显著下降。CMN 预处理可显著预防酶抗氧化剂和线粒体呼吸链酶的活性。CMN 还恢复了肝线粒体中的 LPO 和 PC 含量、GSH 和 NP-SH 水平。
CMN 的摄入可能在化疗期间对奥沙利铂引起的线粒体毒性的调节有效。此外，它被包含在抗癌药物诱导的氧化应激的武器库中。
