Protective effects of hemin in an experimental model of ventilator-induced lung injury

• Published in: European journal of pharmacology 2011-07, Vol.661 (1), p.102-108
• Main Authors: An, Li, Liu, Chang-Ting, Qin, Xue-Bing, Liu, Qing-Hui, Liu, Yan, Yu, Sen-Yang
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Capillary Permeability - drug effects; Cytokines - secretion; Disease Models, Animal; Heme oxygenase-1; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hemin - pharmacology; Inflammation; Male; Mechanical ventilation; Medical sciences; Neutrophil Infiltration - drug effects; Oxidative stress; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Rabbits; RNA, Messenger - genetics; RNA, Messenger - metabolism; Up-Regulation - drug effects; Ventilator-induced lung injury; Ventilator-Induced Lung Injury - genetics; Ventilator-Induced Lung Injury - immunology; Ventilator-Induced Lung Injury - metabolism; Ventilator-Induced Lung Injury - prevention & control
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.04.032

Mechanical ventilation is an indispensable life-support modality for critically ill patients with acute lung injury or acute respiratory distress syndrome. Unfortunately, mechanical ventilation even the protective ventilation strategies may evoke ventilator-induced lung injury. Heme oxygenase-1 (HO-1) has recently exhibited anti-inflammatory and anti-oxidative properties in vitro and in vivo. The effect of HO-1 in ventilator-induced lung injury has not been fully characterized. In this study, rabbits were subjected to high tidal volume ventilation to induce ventilator-induced lung injury, which was confirmed by histopathological alterations, increased bronchoalveolar lavage fluid protein content and lung wet-to-dry ratio. In contrast to the level of HO-1 expression in high tidal volume group, pretreatment with hemin, an inducer of HO-1, further up-regulated HO-1 expression. At the same time, these lung injury indexes were attenuated markedly. This pulmonary protection was accompanied by a decrease in bronchoalveolar lavage fluid neutrophil count and in lung myeloperoxidase activity. Besides, pretreatment with hemin prohibited the production of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-8, and up-regulated the level of anti-inflammatory cytokine interleukin (IL)-10 in bronchoalveolar lavage fluid. Furthermore, a decreased malondialdehyde activity, a marker of oxidative stress and a robust increase in total antioxidant capacity were observed in hemin-treated animals. Our findings suggest that HO-1 up-regulation by hemin plays a protective role in ventilator-induced lung injury by suppression inflammatory process and oxidative stress.