PMID- 27393927 OWN - NLM STAT- MEDLINE DCOM- 20170130 LR - 20170809 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 83 DP - 2016 Oct TI - Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-kappaB related signaling. PG - 302-313 LID - S0753-3322(16)30602-3 [pii] LID - 10.1016/j.biopha.2016.06.036 [doi] AB - 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-1beta), Interleukin 6 (IL-6) and tumor necrosis factor (TNF-alpha), 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. CI - Copyright (c) 2016. Published by Elsevier Masson SAS. FAU - Zhong, Wenhui AU - Zhong W AD - Department of Anesthesiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China. FAU - Qian, Kejian AU - Qian K AD - Department of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China. FAU - Xiong, Jibin AU - Xiong J AD - Department of Hyperbaric Oxygen Therapy, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China. FAU - Ma, Ke AU - Ma K AD - Department of Emergency Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China. FAU - Wang, Aizhong AU - Wang A AD - Department of Anesthesiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China. FAU - Zou, Yan AU - Zou Y AD - Department of Intensive Care Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Pudong 201306, Shanghai, China. Electronic address: zouyan201306@yahoo.com. LA - eng PT - Journal Article DEP - 20160707 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Curcumin/pharmacology/*therapeutic use MH - Hepatic Stellate Cells/drug effects/metabolism/pathology MH - Inflammation/*pathology MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Lipopolysaccharides MH - Liver Failure/*drug therapy/*pathology MH - Male MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - *Oxidative Stress/drug effects MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/genetics/metabolism MH - Reactive Oxygen Species/metabolism MH - Sepsis/blood/*drug therapy MH - *Signal Transduction/drug effects OTO - NOTNLM OT - Apoptosis OT - Curcumin OT - Inflammation OT - Lipopolysaccharides OT - Liver injury OT - Oxidative stress EDAT- 2016/10/25 06:00 MHDA- 2017/01/31 06:00 CRDT- 2016/07/10 06:00 PHST- 2016/05/05 00:00 [received] PHST- 2016/06/14 00:00 [revised] PHST- 2016/06/21 00:00 [accepted] PHST- 2016/10/25 06:00 [pubmed] PHST- 2017/01/31 06:00 [medline] PHST- 2016/07/10 06:00 [entrez] AID - S0753-3322(16)30602-3 [pii] AID - 10.1016/j.biopha.2016.06.036 [doi] PST - ppublish SO - Biomed Pharmacother. 2016 Oct;83:302-313. doi: 10.1016/j.biopha.2016.06.036. Epub 2016 Jul 7.