Isoorientin protects BRL-3A rat liver cell against hydrogen peroxide-induced apoptosis by inhibiting mitochondrial dysfunction, inactivating MAPKs, activating Akt and scavenging ROS and NO

Li Yuan, Xiaomeng Ren, Yuchen Wu, Jing Wang, Haifang Xiao, Xuebo Liu
{"title":"Isoorientin protects BRL-3A rat liver cell against hydrogen peroxide-induced apoptosis by inhibiting mitochondrial dysfunction, inactivating MAPKs, activating Akt and scavenging ROS and NO","authors":"Li Yuan,&nbsp;Xiaomeng Ren,&nbsp;Yuchen Wu,&nbsp;Jing Wang,&nbsp;Haifang Xiao,&nbsp;Xuebo Liu","doi":"10.1016/j.biomag.2013.06.004","DOIUrl":null,"url":null,"abstract":"<div><p><span>Isoorientin<span> (ISO) is a flavonoid compound, and possesses a significant antioxidant potential. However, the effects of ISO on the oxidative damage in normal hepatocytes remain unknown. The present study investigated the protective effects of ISO on H</span></span><sub>2</sub>O<sub>2</sub><span><span>-induced apoptosis in </span>buffalo rat liver (BRL-3A) cells. The results showed that H</span><sub>2</sub>O<sub>2</sub> induced cell death in a dose-dependent manner, pretreatment with ISO significantly (<em>P</em> <!-->&lt;<!--> <span><span>0.01) increased the cell viability in a concentration-dependent manner, and no significant toxicity was found in ISO-treated cells. ISO notably decreased the loss of </span>mitochondrial membrane potential<span> (MMP) and the protein expression of Bax, cytochrome </span></span><em>c</em> (in the cytosol), cleaved caspase-3 and PARP, and ultimately reduced H<sub>2</sub>O<sub>2</sub>-induced BRL-3A cells apoptosis. Meanwhile, ISO also remarkably restrained the activation of ERK1/2, JNK and p38, and the inactivation of Akt induced by H<sub>2</sub>O<sub>2</sub>. Furthermore, ISO significantly reduced H<sub>2</sub>O<sub>2</sub><span>-induced reactive oxygen species<span><span> (ROS) and nitric oxide<span> (NO) production by elevating total superoxide dismutase (T-SOD) and </span></span>catalase<span> (CAT) levels, and inhibiting the expression of inducible nitric oxide synthase (iNOS). These results demonstrated for the first time that ISO is able to protect BRL-3A cells against H</span></span></span><sub>2</sub>O<sub>2</sub><span>-induced apoptosis by inhibiting mitochondrial dysfunction, inactivating MAPK kinases, activating Akt, and scavenging ROS and NO.</span></p></div>","PeriodicalId":100181,"journal":{"name":"Biomedicine & Aging Pathology","volume":"3 3","pages":"Pages 153-159"},"PeriodicalIF":0.0000,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.biomag.2013.06.004","citationCount":"13","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedicine & Aging Pathology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2210522013000312","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 13

Abstract

Isoorientin (ISO) is a flavonoid compound, and possesses a significant antioxidant potential. However, the effects of ISO on the oxidative damage in normal hepatocytes remain unknown. The present study investigated the protective effects of ISO on H2O2-induced apoptosis in buffalo rat liver (BRL-3A) cells. The results showed that H2O2 induced cell death in a dose-dependent manner, pretreatment with ISO significantly (P < 0.01) increased the cell viability in a concentration-dependent manner, and no significant toxicity was found in ISO-treated cells. ISO notably decreased the loss of mitochondrial membrane potential (MMP) and the protein expression of Bax, cytochrome c (in the cytosol), cleaved caspase-3 and PARP, and ultimately reduced H2O2-induced BRL-3A cells apoptosis. Meanwhile, ISO also remarkably restrained the activation of ERK1/2, JNK and p38, and the inactivation of Akt induced by H2O2. Furthermore, ISO significantly reduced H2O2-induced reactive oxygen species (ROS) and nitric oxide (NO) production by elevating total superoxide dismutase (T-SOD) and catalase (CAT) levels, and inhibiting the expression of inducible nitric oxide synthase (iNOS). These results demonstrated for the first time that ISO is able to protect BRL-3A cells against H2O2-induced apoptosis by inhibiting mitochondrial dysfunction, inactivating MAPK kinases, activating Akt, and scavenging ROS and NO.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
异荭草苷通过抑制线粒体功能障碍、灭活MAPKs、激活Akt、清除ROS和NO,保护BRL-3A大鼠肝细胞免受过氧化氢诱导的凋亡
异荭草苷(Isoorientin, ISO)是一种黄酮类化合物,具有显著的抗氧化潜力。然而,ISO对正常肝细胞氧化损伤的影响尚不清楚。本研究探讨了ISO对h2o2诱导的水牛大鼠肝脏(BRL-3A)细胞凋亡的保护作用。结果表明,H2O2诱导细胞死亡呈剂量依赖性,ISO预处理显著(P <0.01)呈浓度依赖性地提高细胞活力,对iso处理的细胞无明显毒性作用。ISO显著降低了线粒体膜电位(MMP)的损失以及Bax、细胞色素c(在细胞质中)、cleaved caspase-3和PARP的蛋白表达,最终减少h2o2诱导的BRL-3A细胞凋亡。同时,ISO还能显著抑制H2O2诱导的ERK1/2、JNK和p38的活化以及Akt的失活。此外,ISO通过提高总超氧化物歧化酶(T-SOD)和过氧化氢酶(CAT)水平,抑制诱导型一氧化氮合酶(iNOS)的表达,显著降低h2o2诱导的活性氧(ROS)和一氧化氮(NO)的产生。这些结果首次证明了ISO能够通过抑制线粒体功能障碍、使MAPK激酶失活、激活Akt、清除ROS和NO来保护BRL-3A细胞免受h2o2诱导的凋亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Glutathione peroxidase-1 expression is up-regulated by ozone therapy in ApoE deficient mice Anticancer effects of vecuronium bromide and cisatracurium besylate on lung cancer cells (A549), in vitro Matricaria Chamomilla extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine Cardioprotective effect of concomitant administration of trigonelline and sitagliptin on cardiac biomarkers, lipid levels, electrocardiographic and heamodynamic modulation on cardiomyopathy in diabetic Wistar rats TDZD-8 pre-treatment in transient middle cerebral artery occlusion
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1