title: Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation.
abstract: Artesunate, a derivative of artemisinin, has anti-inflammatory properties and exerts protective roles in sepsis. Heme oxygense-1 (HO-1) inhibits the inflammatory response through reduction of proinflammatory cytokines and leukocyte influx into tissues. The present study investigated the effects of artesunate on HO-1 and septic lung injury. Cecal ligation and puncture (CLP) was employed to induce septic lung injury. Mice pretreated with artesunate (AS) (15 mg/kg) exhibited decreased sepsis-induced mortality and lung injury and alleviated lung pathological changes and neutrophil infiltration. In addition, AS lowered the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum and bronchoalveolar lavage fluid (BALF) and inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase isoform (iNOS) expression and NF-κB activation in lung tissue. In addition, AS enhanced NF-E2-related factor-2 (Nrf2) activation and HO-1 expression and enzymatic activity in lung tissue. However, the protective effects of AS on sepsis-induced lung injury were eliminated by ZnPP IX, an HO-1 competitive inhibitor. Therefore, AS plays protective roles in septic lung injury related to the upregulation of HO-1. These findings suggest an effective and applicable treatment to sepsis-induced lung injury and provide new insights into the molecular mechanisms and actions of AS.
authors.affiliation: Department of Coronary Care Unit, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Tian-hui
authors.initials: TH
authors.lastname: Cao
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Song-gen
authors.initials: SG
authors.lastname: Jin
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Dong-sheng
authors.initials: DS
authors.lastname: Fei
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Zhi-yuan
authors.initials: ZY
authors.lastname: Lian
authors.affiliation: The Key Hepatosplenic Surgery Laboratory, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shang-ha
authors.initials: SH
authors.lastname: Pan
authors.affiliation: Department of Pediatrics, Children's Hospital of Harbin City, Harbin, China.
authors.forename: Ming-ran
authors.initials: MR
authors.lastname: Zhao
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. mingyan1970@126.com.
authors.forename: Ming-yan
authors.initials: MY
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002432:Cecum / Q000601:surgery; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011524:Protoporphyrins / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D037621:Artemisinins; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C017803:zinc protoporphyrin; D000077332:Artesunate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: acute lung injury; artesunate; heme oxgenase-1; sepsis