Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation

• DOI: 10.1007/s10753-015-0290-2
• Publication Date: 2015-12-01T05:09:48Z
• Authors: Tian-hui Cao; Song-gen Jin; Dong-sheng Fei; Kai Kang; Lei Jiang; Zhi-yuan Lian; Shang-ha Pan; Ming-ran Zhao; Ming-yan Zhao
• Keywords: Male; 0303 health sciences; Interleukin-6; NF-E2-Related Factor 2; Acute Lung Injury; Anti-Inflammatory Agents; NF-kappa B; Artesunate; Nitric Oxide Synthase Type II; Protoporphyrins; Artemisinins; 3. Good health; Enzyme Activation; Mice; 03 medical and health sciences; Neutrophil Infiltration; Cyclooxygenase 2; Sepsis; Animals; Bronchoalveolar Lavage Fluid; Cecum; Lung; Heme Oxygenase-1

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.