title: Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities.
abstract: This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, Yantai, Shandong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Ju-Feng
authors.initials: JF
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, Yantai, Shandong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmacy, Yantai University, Yantai, Shandong, China.
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Fan
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D002460:Cell Line; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D018805:Sepsis / Q000209:etiology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase; D003401:Creatine; C020491:rhein