背景与目的:加速康复外科(ERAS)对外科手术患者的益处已被证实,但是,ERAS对胃癌根治术患者细胞免疫功能及应激反应在分子水平上的影响仍鲜见报道。本研究探讨ERAS理念和措施对腹腔镜胃癌根治术患者肿瘤细胞免疫、炎症因子及应激激素的...背景与目的:加速康复外科(ERAS)对外科手术患者的益处已被证实,但是,ERAS对胃癌根治术患者细胞免疫功能及应激反应在分子水平上的影响仍鲜见报道。本研究探讨ERAS理念和措施对腹腔镜胃癌根治术患者肿瘤细胞免疫、炎症因子及应激激素的影响。方法:纳入2018年1月—2020年12月行腹腔镜胃癌根治术胃癌患者90例,分为ERAS组(43例)和对照组(47例)。ERAS组患者接受ERAS理念行围手术期管理,对照组患者行传统围手术期管理。比较两组在一般资料(性别、年龄、BMI、ASA体格情况评估分级、TNM分期、肿瘤大小),手术相关指标(手术方式、吻合方式、手术时间、术中出血量、淋巴结清扫数)及术后指标(术后下床活动时间、术后肛门首次排气时间、住院时间及术后并发症)的差异。比较两组患者术后1 d及术后7 d两组患者外周血中肿瘤正向免疫调控细胞(CD3+CD4+T细胞、CD3+CD8+T细胞、CD16+CD56+NK细胞);负向免疫调控细胞[中性粒细胞型骨髓源性抑制细胞(G-MDSC)、单核细胞型骨髓源性抑制细胞(M-MDSC)、T-调节细胞(Treg)]及调节性B细胞(Breg)细胞数量百分比,以及两组患者术前及术后24 h应激指标皮质醇(COR)、促肾上腺皮质激素(ACTH)、肾上腺素(EPI)及炎症因子C反应蛋白(CRP)、白细胞介素6(IL-6)水平的差异。结果:ERAS组与对照组在性别、年龄、BMI、ASA分级、TNM分期、肿瘤大小、手术方式、吻合方式、手术时间、术中出血量及淋巴结清扫数方面差异均无统计学意义(均P>0.05)。ERAS组术后下床活动时间和术后肛门首次排气时间均早于对照组(25.01 h vs.37.01 h,P=0.000;74.51 h vs.135.31 h,P=0.000),ERAS组住院时间短于对照组(7.01 d vs.9.81 d,P=0.000)。ERAS组总术后并发症率小于对照组(9.3%vs.19.1%,P=0.027)。在术后1 d及7 d,ERAS组CD3+CD4+T细胞、CD3+CD8+T细胞、CD16+CD56+NK细胞所占百分比高于对照组,而G-MDSC、M-MDSC和Treg细胞及Br展开更多
目的探讨炎症因子白介素-1β(interleukin-1β,IL-1β)对软骨表层细胞(articular cartilage superficial zone cells,ACSCs)衰老的调控作用和相关机制。方法用纤连蛋白黏附法分离培养ACSCs,根据实验分为对照组和IL-1β处理组,采用MTT检...目的探讨炎症因子白介素-1β(interleukin-1β,IL-1β)对软骨表层细胞(articular cartilage superficial zone cells,ACSCs)衰老的调控作用和相关机制。方法用纤连蛋白黏附法分离培养ACSCs,根据实验分为对照组和IL-1β处理组,采用MTT检测细胞增殖情况,衰老相关-β-半乳糖苷酶(SA-β-gal)染色检测SA-β-gal阳性细胞数,Western blot检测p21和p53蛋白水平,实时荧光定量PCR(RT-qPCR)检测衰老相关分泌表型(senescence-associated secretory phenotype,SASP)因子il-6、Mmp-3和Mmp-13 m RNA水平,CellROX试剂检测活性氧(reactive oxygen species,ROS)水平,JC-1试剂检测线粒体膜电位。最后,取ACSCs设IL-1β处理组和IL-1β+N-乙酰半胱氨酸(N-acetylcysteine,NAC)处理组,检测NAC处理后对IL-1β引起的细胞ROS水平、细胞增殖、SA-β-gal阳性细胞数、p21和p53蛋白水平和SASP分泌因子水平的影响。结果IL-1β处理导致ACSCs出现衰老相关表型,包括增殖减慢(P<0.05)、SA-β-gal染色阳性细胞增加(P<0.05)、p53和p21蛋白水平升高(P<0.05)、SASP因子il-6、Mmp-13和Mmp-3 m RNA水平升高(P<0.05)。进一步研究发现,IL-1β可以导致ACSCs中线粒体膜电位降低(P<0.05),ROS增加(P<0.05),而采用抗氧化剂NAC处理可以明显缓解IL-1β导致的ACSCs中ROS增加和ACSCs衰老相关表型(P<0.05)。结论IL-1β通过诱导氧化应激促进ACSCs衰老,这为从抑制ACSCs衰老和拮抗ACSCs氧化应激损伤角度治疗骨关节炎提供了实验依据。展开更多
背景:靶向铁过载基因调节铁死亡或许是一种较快且有效延缓骨关节炎退变的方法,但目前对骨关节炎铁死亡相关分子机制及基因靶点尚不清楚。目的:通过生物信息学分析铁死亡在骨关节炎中的关键基因和途径,结合体外实验验证骨关节炎中铁死亡...背景:靶向铁过载基因调节铁死亡或许是一种较快且有效延缓骨关节炎退变的方法,但目前对骨关节炎铁死亡相关分子机制及基因靶点尚不清楚。目的:通过生物信息学分析铁死亡在骨关节炎中的关键基因和途径,结合体外实验验证骨关节炎中铁死亡标记基因,探讨铁死亡在骨关节炎中的潜在作用。方法:以“Osteoarthritis”为检索词,通过GEO数据库检索2010-01-01/2021-01-01的公开数据,筛选得到基因微阵列数据集GSE55235,对GSE55235数据集进行数据矫正后分析获得差异表达基因;利用FerrDb数据库检索得到铁死亡相关基因与GSE55235数据集差异表达基因作交集,对交集基因作基因本体(Gene Ontology,GO)与京都基因和基因组数据库富集分析(Kyoto Encyclopedia of Genes and Genomes,KEGG)并绘制蛋白质-蛋白质相互作用网络,获得骨关节炎铁死亡HUB基因,筛选出铁死亡标记基因;将正常人软骨细胞设为对照组、人软骨细胞骨关节炎模型设为实验组,采用实时荧光定量PCR对两组铁死亡标记基因的mRNA表达进行验证。结果与结论:①共获得36个骨关节炎铁死亡基因,GO富集分析表明其主要参与氧化应激反应、皮质类固醇反应、类固醇激素反应、对糖皮质激素的反应和活性氧的代谢等过程;②针对产生超氧化物的NAD(P)H氧化酶及氧化还原酶活性、血红素结合、四吡咯结合中发挥作用;③KEGG富集分析表明骨关节炎铁死亡基因主要参与NOD样受体、白细胞介素17、缺氧诱导因子1、肿瘤坏死因子及叉头盒O类(FoxO)等信号通路;④构建蛋白质-蛋白质相互作用网络,进一步分析获得血管内皮生长因子A、白细胞介素6、JUN、PTGS2和DUSP1等5个骨关节炎铁死亡HUB基因,筛选出血管内皮生长因子A、白细胞介素6、PTGS2和DUSP1等4个铁死亡标记基因,体外实验证实其在对照组(正常人软骨细胞)与实验组(细胞骨关节炎模型)中有显著差异(P展开更多
背景:帕金森病是全球第二大神经退行性疾病,其运动症状和非运动症状都严重影响患者日常生活,最近研究发现外泌体及其携带的物质参与帕金森病病理发生发展,且还介导细胞通讯可作为帕金森病的潜在生物标志物。目的:探讨外泌体介导细胞通...背景:帕金森病是全球第二大神经退行性疾病,其运动症状和非运动症状都严重影响患者日常生活,最近研究发现外泌体及其携带的物质参与帕金森病病理发生发展,且还介导细胞通讯可作为帕金森病的潜在生物标志物。目的:探讨外泌体介导细胞通讯作为帕金森病的潜在生物标志物的类型及其发生作用的机制,用以寻找新的早期诊疗靶点,以期减缓帕金森病的发病进程并为其诊疗提供新思路。方法:应用计算机检索1987年1月至2022年8月PubMed、中国知网、万方数据、维普、Web of Science、EMBASE、Cochrane、EBSCO和SinoMed数据库收录的相关文献,最终纳入76篇英文文献和2篇中文文献进行归纳分析。结果与结论:(1)外泌体通过胞吞胞吐膜融合方式输送物质至受体细胞或膜表面携带信号因子,释放在细胞间隙等方式在细胞间通讯进行物质交换。(2)外泌体可通过介导细胞间通讯和信息交流以及物质运输参与帕金森病的病理进展,因此其可作为帕金森病的早期生物标志物,协助提供新的诊疗靶点,并可作为将来帕金森病的诊疗载体。(3)外泌体通过细胞间传递和物质运输扩散介导参与帕金森病病理发展机制,其主要生物标志物与病理作用途径的关系为:外泌体α突触核蛋白介导神经毒性、神经炎症、氧化应激及细胞自噬等过程,外泌体微小RNA可以靶向帕金森病相关基因并参与氧化应激,外泌体DJ-1蛋白调控细胞的氧化应激水平并影响细胞毒性,外泌体富含亮氨酸的重复激酶2介导路易体形成和堆积造成神经毒性,以上外泌体及其携带物质均可作为帕金森病的早期生物标志物。(4)目前外泌体的帕金森病生物标志物相关研究较少,但其中最具代表性和应用最多的是外泌体α突触核蛋白,由于外泌体微小RNA种类多数量大,在帕金森病中表达和作用不尽相同,近两年成为了研究热点。(5)目前相关展开更多
Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as e...Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.展开更多
Background/Aim We investigated the relationship between ethanol exposure and heme oxygenase (HO-1) in human hepatocytes in order to ascertain if induction of HO-1 can prevent ethanol induced cellular damage. Methods...Background/Aim We investigated the relationship between ethanol exposure and heme oxygenase (HO-1) in human hepatocytes in order to ascertain if induction of HO-1 can prevent ethanol induced cellular damage. Methods Dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) ethanol exposure were used in the present study. HO-1 mRNA and protein expression were detected by PT-PCR and Western blot respectively. HO-1 activity was indicated by bilirubin and Fe2+ formation. Cytotoxicity was investigated by means of lactate dehydrogenate (LDH) and aspartate transaminase (AST) level in culture supernatants, as well as the intracellular formation of malondialdehyde (MDA), cellular glutathione (GSH) status and CYP 2E1 activity. Results We first demonstrated a dose-dependent response between ethanol exposure and HO-1 mRNA and protein expression in human hepatocytes. We further observed a time-dependent increase of HO-1 mRNA expression using 100 mmol/L ethanol starting 30 minutes after ethanol exposure, reaching its maximum between 3 h and 9 h. Being similar to what had been demonstrated with the mRNA level, increased protein expression started at 6 h after ethanol exposure, and kept continuous elevated over 18 h. In addition, we found that ethanol exposure to hepatocytes markedly increased HO-1 enzyme activity in a time-dependent manner measured as bilirubin and Fe2+ formation in human hepatocytes. Our results clearly showed that ethanol exposure caused a significant increase of LDH, AST, and MDA levels, while the antioxidant GSH was time-dependently reduced. Furthermore, we demonstrated that pre-administration of cobalt protoporphyrin (CoPP) induced HO-1 in human hepatocytes, and prevented an increase of MDA and a decrease of GSH. These effects could be partially reversed by zinc protoporphyrin (ZnPP), an antagonist of HO-1 induction. Conclusion HO-1 expression in cells or organs could lead to new strategies for better prevention and treatment of ethanol-induced oxidative damage in human liver.展开更多
文摘背景与目的:加速康复外科(ERAS)对外科手术患者的益处已被证实,但是,ERAS对胃癌根治术患者细胞免疫功能及应激反应在分子水平上的影响仍鲜见报道。本研究探讨ERAS理念和措施对腹腔镜胃癌根治术患者肿瘤细胞免疫、炎症因子及应激激素的影响。方法:纳入2018年1月—2020年12月行腹腔镜胃癌根治术胃癌患者90例,分为ERAS组(43例)和对照组(47例)。ERAS组患者接受ERAS理念行围手术期管理,对照组患者行传统围手术期管理。比较两组在一般资料(性别、年龄、BMI、ASA体格情况评估分级、TNM分期、肿瘤大小),手术相关指标(手术方式、吻合方式、手术时间、术中出血量、淋巴结清扫数)及术后指标(术后下床活动时间、术后肛门首次排气时间、住院时间及术后并发症)的差异。比较两组患者术后1 d及术后7 d两组患者外周血中肿瘤正向免疫调控细胞(CD3+CD4+T细胞、CD3+CD8+T细胞、CD16+CD56+NK细胞);负向免疫调控细胞[中性粒细胞型骨髓源性抑制细胞(G-MDSC)、单核细胞型骨髓源性抑制细胞(M-MDSC)、T-调节细胞(Treg)]及调节性B细胞(Breg)细胞数量百分比,以及两组患者术前及术后24 h应激指标皮质醇(COR)、促肾上腺皮质激素(ACTH)、肾上腺素(EPI)及炎症因子C反应蛋白(CRP)、白细胞介素6(IL-6)水平的差异。结果:ERAS组与对照组在性别、年龄、BMI、ASA分级、TNM分期、肿瘤大小、手术方式、吻合方式、手术时间、术中出血量及淋巴结清扫数方面差异均无统计学意义(均P>0.05)。ERAS组术后下床活动时间和术后肛门首次排气时间均早于对照组(25.01 h vs.37.01 h,P=0.000;74.51 h vs.135.31 h,P=0.000),ERAS组住院时间短于对照组(7.01 d vs.9.81 d,P=0.000)。ERAS组总术后并发症率小于对照组(9.3%vs.19.1%,P=0.027)。在术后1 d及7 d,ERAS组CD3+CD4+T细胞、CD3+CD8+T细胞、CD16+CD56+NK细胞所占百分比高于对照组,而G-MDSC、M-MDSC和Treg细胞及Br
文摘目的探讨炎症因子白介素-1β(interleukin-1β,IL-1β)对软骨表层细胞(articular cartilage superficial zone cells,ACSCs)衰老的调控作用和相关机制。方法用纤连蛋白黏附法分离培养ACSCs,根据实验分为对照组和IL-1β处理组,采用MTT检测细胞增殖情况,衰老相关-β-半乳糖苷酶(SA-β-gal)染色检测SA-β-gal阳性细胞数,Western blot检测p21和p53蛋白水平,实时荧光定量PCR(RT-qPCR)检测衰老相关分泌表型(senescence-associated secretory phenotype,SASP)因子il-6、Mmp-3和Mmp-13 m RNA水平,CellROX试剂检测活性氧(reactive oxygen species,ROS)水平,JC-1试剂检测线粒体膜电位。最后,取ACSCs设IL-1β处理组和IL-1β+N-乙酰半胱氨酸(N-acetylcysteine,NAC)处理组,检测NAC处理后对IL-1β引起的细胞ROS水平、细胞增殖、SA-β-gal阳性细胞数、p21和p53蛋白水平和SASP分泌因子水平的影响。结果IL-1β处理导致ACSCs出现衰老相关表型,包括增殖减慢(P<0.05)、SA-β-gal染色阳性细胞增加(P<0.05)、p53和p21蛋白水平升高(P<0.05)、SASP因子il-6、Mmp-13和Mmp-3 m RNA水平升高(P<0.05)。进一步研究发现,IL-1β可以导致ACSCs中线粒体膜电位降低(P<0.05),ROS增加(P<0.05),而采用抗氧化剂NAC处理可以明显缓解IL-1β导致的ACSCs中ROS增加和ACSCs衰老相关表型(P<0.05)。结论IL-1β通过诱导氧化应激促进ACSCs衰老,这为从抑制ACSCs衰老和拮抗ACSCs氧化应激损伤角度治疗骨关节炎提供了实验依据。
文摘背景:靶向铁过载基因调节铁死亡或许是一种较快且有效延缓骨关节炎退变的方法,但目前对骨关节炎铁死亡相关分子机制及基因靶点尚不清楚。目的:通过生物信息学分析铁死亡在骨关节炎中的关键基因和途径,结合体外实验验证骨关节炎中铁死亡标记基因,探讨铁死亡在骨关节炎中的潜在作用。方法:以“Osteoarthritis”为检索词,通过GEO数据库检索2010-01-01/2021-01-01的公开数据,筛选得到基因微阵列数据集GSE55235,对GSE55235数据集进行数据矫正后分析获得差异表达基因;利用FerrDb数据库检索得到铁死亡相关基因与GSE55235数据集差异表达基因作交集,对交集基因作基因本体(Gene Ontology,GO)与京都基因和基因组数据库富集分析(Kyoto Encyclopedia of Genes and Genomes,KEGG)并绘制蛋白质-蛋白质相互作用网络,获得骨关节炎铁死亡HUB基因,筛选出铁死亡标记基因;将正常人软骨细胞设为对照组、人软骨细胞骨关节炎模型设为实验组,采用实时荧光定量PCR对两组铁死亡标记基因的mRNA表达进行验证。结果与结论:①共获得36个骨关节炎铁死亡基因,GO富集分析表明其主要参与氧化应激反应、皮质类固醇反应、类固醇激素反应、对糖皮质激素的反应和活性氧的代谢等过程;②针对产生超氧化物的NAD(P)H氧化酶及氧化还原酶活性、血红素结合、四吡咯结合中发挥作用;③KEGG富集分析表明骨关节炎铁死亡基因主要参与NOD样受体、白细胞介素17、缺氧诱导因子1、肿瘤坏死因子及叉头盒O类(FoxO)等信号通路;④构建蛋白质-蛋白质相互作用网络,进一步分析获得血管内皮生长因子A、白细胞介素6、JUN、PTGS2和DUSP1等5个骨关节炎铁死亡HUB基因,筛选出血管内皮生长因子A、白细胞介素6、PTGS2和DUSP1等4个铁死亡标记基因,体外实验证实其在对照组(正常人软骨细胞)与实验组(细胞骨关节炎模型)中有显著差异(P
文摘背景:帕金森病是全球第二大神经退行性疾病,其运动症状和非运动症状都严重影响患者日常生活,最近研究发现外泌体及其携带的物质参与帕金森病病理发生发展,且还介导细胞通讯可作为帕金森病的潜在生物标志物。目的:探讨外泌体介导细胞通讯作为帕金森病的潜在生物标志物的类型及其发生作用的机制,用以寻找新的早期诊疗靶点,以期减缓帕金森病的发病进程并为其诊疗提供新思路。方法:应用计算机检索1987年1月至2022年8月PubMed、中国知网、万方数据、维普、Web of Science、EMBASE、Cochrane、EBSCO和SinoMed数据库收录的相关文献,最终纳入76篇英文文献和2篇中文文献进行归纳分析。结果与结论:(1)外泌体通过胞吞胞吐膜融合方式输送物质至受体细胞或膜表面携带信号因子,释放在细胞间隙等方式在细胞间通讯进行物质交换。(2)外泌体可通过介导细胞间通讯和信息交流以及物质运输参与帕金森病的病理进展,因此其可作为帕金森病的早期生物标志物,协助提供新的诊疗靶点,并可作为将来帕金森病的诊疗载体。(3)外泌体通过细胞间传递和物质运输扩散介导参与帕金森病病理发展机制,其主要生物标志物与病理作用途径的关系为:外泌体α突触核蛋白介导神经毒性、神经炎症、氧化应激及细胞自噬等过程,外泌体微小RNA可以靶向帕金森病相关基因并参与氧化应激,外泌体DJ-1蛋白调控细胞的氧化应激水平并影响细胞毒性,外泌体富含亮氨酸的重复激酶2介导路易体形成和堆积造成神经毒性,以上外泌体及其携带物质均可作为帕金森病的早期生物标志物。(4)目前外泌体的帕金森病生物标志物相关研究较少,但其中最具代表性和应用最多的是外泌体α突触核蛋白,由于外泌体微小RNA种类多数量大,在帕金森病中表达和作用不尽相同,近两年成为了研究热点。(5)目前相关
基金supported by the Basic Study and Interdisciplinary R&D Foundation of the University of Seoul(2019)grants,Nos.201910021035202006251003(both to KYR and JC)。
文摘Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.
基金This work was supported by the National Natural Science Foundation of China (NSFC) (30271130).
文摘Background/Aim We investigated the relationship between ethanol exposure and heme oxygenase (HO-1) in human hepatocytes in order to ascertain if induction of HO-1 can prevent ethanol induced cellular damage. Methods Dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) ethanol exposure were used in the present study. HO-1 mRNA and protein expression were detected by PT-PCR and Western blot respectively. HO-1 activity was indicated by bilirubin and Fe2+ formation. Cytotoxicity was investigated by means of lactate dehydrogenate (LDH) and aspartate transaminase (AST) level in culture supernatants, as well as the intracellular formation of malondialdehyde (MDA), cellular glutathione (GSH) status and CYP 2E1 activity. Results We first demonstrated a dose-dependent response between ethanol exposure and HO-1 mRNA and protein expression in human hepatocytes. We further observed a time-dependent increase of HO-1 mRNA expression using 100 mmol/L ethanol starting 30 minutes after ethanol exposure, reaching its maximum between 3 h and 9 h. Being similar to what had been demonstrated with the mRNA level, increased protein expression started at 6 h after ethanol exposure, and kept continuous elevated over 18 h. In addition, we found that ethanol exposure to hepatocytes markedly increased HO-1 enzyme activity in a time-dependent manner measured as bilirubin and Fe2+ formation in human hepatocytes. Our results clearly showed that ethanol exposure caused a significant increase of LDH, AST, and MDA levels, while the antioxidant GSH was time-dependently reduced. Furthermore, we demonstrated that pre-administration of cobalt protoporphyrin (CoPP) induced HO-1 in human hepatocytes, and prevented an increase of MDA and a decrease of GSH. These effects could be partially reversed by zinc protoporphyrin (ZnPP), an antagonist of HO-1 induction. Conclusion HO-1 expression in cells or organs could lead to new strategies for better prevention and treatment of ethanol-induced oxidative damage in human liver.
