Waseem Mohammad, Tabassum Heena, Bhardwaj Monica, Parvez Suhel
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Department of Biochemistry, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Mol Med Rep. 2017 Sep;16(3):2939-2945. doi: 10.3892/mmr.2017.6860. Epub 2017 Jun 27.
The present study aimed to investigate the hepatoprotective effects of the bioflavonoid quercetin (QR) on cisplatin (CP)‑induced mitochondrial oxidative stress in the livers of rats, to elucidate the role of mitochondria in CP‑induced hepatotoxicity, and its underlying mechanism. Isolated liver mitochondria were incubated with 100 µg/ml CP and/or 50 µM QR in vitro. CP treatment triggered a significant increase in membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, and a decrease in reduced glutathione (GSH) and non‑protein thiol (NP‑SH) levels. In addition, CP caused a marked decline in the activities of enzymatic antioxidants and mitochondrial complexes (I, II, III and V) in liver mitochondria. QR pre‑treatment significantly modulated the activities of enzymatic antioxidants and mitochondrial complex enzymes. Furthermore, QR reversed the alterations in LPO and PC levels, and GSH and NP‑SH contents in liver mitochondria. The results of the present study suggested that QR supplementation may suppress CP‑induced mitochondrial toxicity during chemotherapy, and provides a potential prophylactic and defensive candidate for anticancer agent‑induced oxidative stress.
本研究旨在探讨生物类黄酮槲皮素（QR）对顺铂（CP）诱导的大鼠肝脏线粒体氧化应激的肝保护作用，阐明线粒体在CP诱导的肝毒性中的作用及其潜在机制。分离的肝线粒体在体外与100μg/ml CP和/或50μM QR孵育。CP处理导致膜脂质过氧化（LPO）水平、蛋白质羰基（PC）含量显著增加，还原型谷胱甘肽（GSH）和非蛋白质硫醇（NP-SH）水平降低。此外，CP导致肝线粒体中酶抗氧化剂和线粒体复合物（I、II、III和V）的活性显著下降。QR预处理显著调节了酶抗氧化剂和线粒体复合酶的活性。此外，QR逆转了肝线粒体中LPO和PC水平以及GSH和NP-SH含量的变化。本研究结果表明，补充QR可能在化疗期间抑制CP诱导的线粒体毒性，并为抗癌药物诱导的氧化应激提供一种潜在的预防和防御候选药物。
