Wali Adil Farooq, Rashid Summya, Rashid Shahzada Mudasir, Ansari Mushtaq Ahmad, Khan Mohammad Rashid, Haq Nazrul, Alhareth Dhafer Yahya, Ahmad Ajaz, Rehman Muneeb U
RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, UAE.
Department of Pharmacology & Toxicology, College of Pharmacy Girls Section, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.
Plants (Basel). 2020 Apr 24;9(4):550. doi: 10.3390/plants9040550.
Doxorubicin (Dox) is an operational and largely used anticancer drug, used to treat an array of malignancies. Nonetheless, its beneficial use is constrained due to its renal and hepatotoxicity dose dependently. Numerous research findings favor the use of antioxidants may impact Dox-induced liver injury/damage. In the current study, Wistar rats were given naringenin (50 and 100 mg/kg b.wt.) orally for 20 days as prophylactic dose, against the hepatotoxicity induced by single intraperitoneal injection of Dox (20 mg/kg b.wt.). Potency of naringenin against the liver damage caused by Dox was assessed by measuring malonyl aldehyde (MDA) as a by-product of lipid peroxidation, biochemical estimation of antioxidant enzyme system, reactive oxygen species (ROS) level, and inflammatory mediators. Naringenin-attenuated ROS production, ROS-induced lipid peroxidation, and replenished reduced antioxidant armory, namely, catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). Naringenin similarly diminished expression of Cox-2 and levels of NF-κB and other inflammatory molecules induced by the Dox treatment. Histology added further evidence to the defensive effects of naringenin on Dox-induced liver damage. The outcomes of the current study reveal that oxidative stress and inflammation are meticulously linked with Dox-triggered damage, and naringenin illustrates the potential effect on Dox-induced hepatotoxicity probably through diminishing the oxidative stress and inflammation.
阿霉素（Dox）是一种常用的抗癌药物，用于治疗一系列恶性肿瘤。然而，由于其肾毒性和肝毒性呈剂量依赖性，其有益用途受到限制。许多研究结果表明，使用抗氧化剂可能会影响阿霉素诱导的肝损伤。在本研究中，将Wistar大鼠口服给予柚皮素（50和100mg/kg体重），持续20天作为预防剂量，以对抗单次腹腔注射阿霉素（20mg/kg体重）诱导的肝毒性。通过测量脂质过氧化副产物丙二醛（MDA）、抗氧化酶系统的生化评估、活性氧（ROS）水平和炎症介质来评估柚皮素对阿霉素引起的肝损伤的效力。柚皮素可减轻ROS产生、ROS诱导的脂质过氧化，并补充减少的抗氧化剂储备，即过氧化氢酶（CAT）、谷胱甘肽还原酶（GR）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽（GSH）。柚皮素同样降低了阿霉素治疗诱导的Cox-2表达以及NF-κB和其他炎症分子的水平。组织学进一步证明了柚皮素对阿霉素诱导的肝损伤的防御作用。本研究结果表明，氧化应激和炎症与阿霉素引发的损伤密切相关，柚皮素可能通过减轻氧化应激和炎症对阿霉素诱导的肝毒性具有潜在作用。
