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, Xiaomeng Ren, Yuchen Wu, Jing Wang, Haifang Xiao, 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> <!--><<!--> <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.