Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney
Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney
复制标题
油橄榄叶提取物上调Nrf2/ARE/HO-1信号转导并减轻环磷酰胺诱导的大鼠肾脏氧化应激、炎症和细胞凋亡
DOI：
10.1016/j.biopha.2018.12.112
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发表时间：
2019-03-01
影响因子：
7.5
通讯作者：
Mahmoud, Ayman M.
中科院分区：
文献类型：
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作者：
ALHaithloul, Haifa A. S.;Alotaibi, Mohammed F.;Mahmoud, Ayman M.
橄榄叶提取物（OLE）具有潜在的健康益处，并保护不同器官免受细胞毒性。然而，尚无关于其预防环磷酰胺（CP）引起的肾毒性的报道。本研究从氧化应激、炎症、细胞凋亡和Nrf2/ARE/HO-1信号通路等方面探讨了OLE对cp所致大鼠肾损伤可能的保护作用。大鼠给予100或200 mg/kg体重的OLE治疗15 d，第16天单次注射150 mg/kg CP。CP引起的肾损伤表现为血清肌酐和尿素显著升高，组织病理改变包括肾小球萎缩、间质出血、尿腔扩张和坏死。cp诱导大鼠肾脂质过氧化、蛋白羰基、一氧化氮（NO）和促炎细胞因子升高，nf - κ B、Bax、细胞色素c和caspase-3上调。OLE可改善肾功能指标，防止cp诱导的组织损伤。此外，OLE通过增强抗氧化防御和Bcl-2表达，抑制促炎和促凋亡标志物NF-kappa B、Bax、细胞色素c和caspase-3，显著预防氧化应激、炎症和凋亡。OLE上调cp诱导大鼠肾脏中Nrf2、HO-1和NQO-1的表达。综上所述，OLE通过上调Nrf2/ARE/HO-1信号，增强抗氧化活性，减轻炎症和细胞凋亡，对cp诱导的大鼠肾毒性具有重要的保护作用。
Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-kappa B, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-kappa B, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis.