title: Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling.
abstract: In many liver disorders, oxidative stress-related inflammation and apoptosis are important pathogenic components, finally resulting in acute liver failure. Erythropoietin and its analogues are well known to influence the interaction between apoptosis and inflammation in brain and kidney. The study is to clarify the effect of curcumin, a natural plant phenolic food additive, on lipopolysaccharides (LPS)-induced acute liver injury of mice with endotoxemia and associated molecular mechanism from inflammation, apoptosis and oxidative stress levels. And curcumin, lowered serum cytokines, including Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and tumor necrosis factor (TNF-α), and improved liver apoptosis through suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibiting Cyclic AMP-responsive element-binding protein (CREB)/Caspase expression, and decreased oxidative stress-associated protein expression, mainly involving 2E1 isoform of cytochrome P450/nuclear factor E2-related factor 2/reactive oxygen species (CYP2E/Nrf2/ROS) signaling pathway, as well as liver nitric oxide (NO) production in LPS-induced mice. Moreover, curcumin regulated serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), accelerated liver antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-px) levels, and inhibited activation of the mitogen-activated protein kinases/c-Jun NH2-terminal kinase (P38/JNK) cascade in the livers of LPS-induced rats. Thus, curcumin treatment attenuates LPS-induced PI3K/AKT and CYP2E/Nrf2/ROS signaling and liver injury. Strategies to inhibit inflammation and apoptosis signaling may provide alternatives to the current clinical approaches to improve oxidative responses of endotoxemia.
authors.affiliation: Department of Anesthesiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Qian
authors.affiliation: Department of Hyperbaric Oxygen Therapy, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Emergency Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China.
authors.forename: Aizhong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China. Electronic address: zouyan201306@yahoo.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D017093:Liver Failure / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Apoptosis; Curcumin; Inflammation; Lipopolysaccharides; Liver injury; Oxidative stress