Protective Effect of Resveratrol on Acute Lung Injury Induced by Lipopolysaccharide in Mice

Abstract

Resveratrol, a phytoalexin found in a range of plant products, may exert a variety of pharmacological activities. In this study, we investigated the effect of resveratrol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we found that the pretreatment with resveratrol can effectively protect mice against LPS-induced ALI. Mice were pretreated with 1 mg/kg resveratrol for 3 days before challenging with a dose of 15 mg/ kg LPS. The histological result showed that resveratrol can suppress the edema, inflammatory cell infiltration, and alveolar structure damage of lungs in ALI mice, and a decrease in the lung W/D ratio was also observed in mice with resveratrol pretreatment. Additionally, resveratrol markedly decreased the production of inflammatory cytokines, including IL-1b and MIP-1a and prevented the release of nitric oxide (NO) through inhibiting the expression of inducible NO synthase in lung tissues. Furthermore, the pretreatment with resveratrol suppressed the nuclear translocation of NFjB in lung tissues, which may be partly responsible for its effect on the ALI. In conclusion, the results presented here may suggest resveratrol as a potential therapeutic agent for treating ALI in the future. Anat Rec, 294:527-532, 2011. V V C 2011 Wiley-Liss, Inc.Key words: resveratrol; acute lung injury; lipopolysaccharide; NF-jB Acute lung injury (ALI) is a common clinical problem, which is characterized by the upregulation of inflammatory mediators in the host and followed by an onset of dyspnea, severe hypoxemia, and pulmonary edema, thus leading to significant morbidity and mortality (Erickson et al., 2009;Martinez et al., 2009). Several animal models have been developed to study the pathophysiologic mechanism involved in ALI, and the intraperitoneal injection of lipopolysaccharide (LPS), a component of the outer cell wall of most gram-negative bacteria, is one of the most common accepted models. ALI represents a state of excess production of inflammatory mediators, including cytokines, chemokines, and adhesion molecules (Ware and Matthay, 2000); and the release of LPS is a major stimulus for release of cytokines, which may further cause pulmonary damage leading to ALI (Ware et al., 2007). Although great advances in understanding the pathophysiology of ALI had been achieved, the available therapies have not reduced the mortality or increased the quality of life in survivors.Upregulation of inducible nitric oxide synthase (iNOS) increased the production of nitric oxide (NO), which was observed in ALI both in animal models and humans

Resveratrol Protects against Cigarette Smoke–Induced Oxidative Damage and Pulmonary Inflammation

“…Our results showed that resveratrol inhibited the translocation of p65 NF-κB into nucleus and suppressed NF-κB DNA binding activity in a dosedependent manner, indicating that resveratrol exerts anti-inflammatory effects that might be through inhibition of NF-κB activation. Similar effects of resveratrol have been observed in LPS-induced lung injury [28]. Thus, inhibition of NF-κB provides one possible mechanism for the resveratrol-mediated anti-inflammatory activity.…”

Hydrogen-rich saline ameliorates lung injury associated with cecal ligation and puncture-induced sepsis in rats

“…Although LPS is the most important pathogen that leads to the development of ALI and intra-tracheal instillation of LPS has been commonly used to induce an animal model of ALI (Cao et al, 2011;El-Agamy, 2011), the CLP model seems to resemble qualitatively as well as quantitatively the clinical observations of vascular reactivity and inflammation in the lung during polymicrobial peritonitis, bacteremia, and systemic sepsis (Riedemann et al, 2003). So we Fig.…”

Hydrogen inhalation ameliorates lipopolysaccharide-induced acute lung injury in mice

“…LPS is the most important pathogen that leads to the development of ALI and intra-tracheal instillation of LPS has been commonly used to induce an animal model of ALI [24,25], so we established an ALI mice model through intra-tracheal injection of LPS (5 mg/kg) in our present study. The increased production of free radicals combined with decreased antioxidant capacity of pulmonary vascular tissue contributes to the prognosis of LPS-induced ALI.…”