Abstract
Alpha-linolenic acid (ALA), an important component of polyunsaturated fatty acids (PUFAs), possesses potent anti-inflammatory properties. To date, the effects of ALA on acute lung injury (ALI) remains unknown. This study was designed to investigate the potential protective effects of ALA on LPS-induced ALI and the underpinning mechanisms. An animal model of ALI was established via intratracheally injection of lipopolysaccharide (LPS, 1 mg/kg). We found that lung wet/dry weight ratio and protein concentration in Bronchoalveolar lavage fluid (BALF) were dramatically decreased by ALA pretreatment. Treatment with ALA significantly alleviated the infiltration of total cells and neutrophils, while increased the number of the macrophages. ALA significantly inhibited the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and increased anti-inflammatory cytokine. Moreover, we found that the levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were highly increased in LPS-induced ALI, while the activities of glutathione (GSH) and superoxide dismutase (SOD) were decreased, which were reversed by ALA. ALA attenuated LPS-induced histopathological changes and apoptosis. Furthermore, ALA significantly inhibited the phosphorylation of IκBα and NF-κB (p65) activation in ALI. ALA showed anti-inflammatory effects in mice with LPS-induced ALI. NF-κB pathway may be involved in ALA mediated protective effects.
Link to Full Text
Key Points
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are the leading causes of mortality in critically ill patients. The pathogenesis of ALI is characterized by rapid onset pulmonary edema, hypoxemia, alveolar-capillary barrier damage, inflammatory cells recruitment, uncontrolled oxidative stress and a cascade of inflammatory process. ALA has been reported to exhibit potent anti-inflammatory properties. ALA down-regulated inflammatory iNOS, COX-2, and TNF-α gene expressions through the inhibition of NF-κB and MAPKs pathways [11]. PUFAs can also inhibit ROS and RNS formation and may participate in the regulation of enzymes responsible for reactive species production. The purpose of this study was to evaluate the potential protective effects of ALA in an animal model of LPS-induced ALI and elucidate the potential molecular mechanisms. It is believed that ALA regulates inflammatory response by down-regulating pro-inflammatory eicosanoids. ALA abated the apoptotic cells of lungs in LPS-induced acute lung injury. Lung tissues were harvested 6 h after LPS administration. ALA pretreatment effectively supressed the phosphorylation of LPS, the outer membrane component of Gram-negative bacteria, can trigger the generation of a series of inflammatory mediators and reactive oxygen. The study revealed that intratracheally injection of LPS resulted in the destruction of alveolar structure and pulmonary edema, which was in accordance with the previous research. ALA exhibited substantial protective effects against LPS-induced ALI, as evidenced by alleviated pathologic injuries and pulmonary edema. ALA could inhibit the neutrophils recruitment induced by LPS. The results indicated that LPS administrated intratracheally induced a decline in macrophages, but ALA treatment inhibited this downtrend. ALA significantly inhibited LPS-induced the production of TNF-α, IL-6 and IL-1β in BALF. Pre-treatment with a high concentration of ALA markedly increased the secretion of IL-10. The present results indicate that the actions of ALA to alleviate ALI are associated with its anti-inflammatory activity. In conclusion, the results demonstrated that ALA exhibited a remarkable protective effects on ALI through the attenuation of inflammatory cytokines, oxidative stress and apoptosis. ALA may also have a potential therapeutic effect on the patients with ALI.