Folic Acid Supplementation Reversed Lung Inflammatory Response, Oxidative Damage and Histopathological Alterations in an LPS-Induced Rat Model of Lung Injury

Aim: Lipopolysaccharide (LPS) induced systemic inflammation is a well-known experimental model for studying damage to various organs, and the lungs are known to be one of the targets of the detrimental effects of inflammatory processes. Activation of specific signaling pathways such as LPS /Toll-like receptor (TLR)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kβ) induces an inflammatory response and impairs the function of the respiratory system. Folic acid (FA) is a water-soluble vitamin that plays a special role in biological processes such as cell division. Limited studies have evaluated the lung protective effects of folic acid. Therefore, we conducted this preclinical study to demonstrate the lung protective effect of FA and its possible mechanisms in LPS-induced lung injury. Material and Methods: Rats were divided into five groups (n =10 in each group): a normal control group, LPS challenged group treated with saline, and three group challenged with LPS and treated with FA (5.10, and 20 mg/kg). Rats were treated with FA for three weeks, and in the third week, LPS was injected daily after FA administration. Lung inflammatory response and oxidative stress biomarkers as well as histopathological status was assessed in the end of study. Data were analyzed using Prism version 8 using one-way ANOVA with Tukey’s post hoc tests. Results: FA supplementation resulted in markedly decreased lipid peroxidation level and increased superoxide dismutase (SOD), catalase (CAT) and thiol activity both in the lung and broncho-alveolar lavage fluid (BALF) (P< 0.05 to P< 0.001). Treatment with FA also reduced lung inflammatory response by reversing increased total and differential white blood cells (WBC) counts (P< 0.05 to P< 0.001). Also, FA administration improved lung histopathological change (P< 0.01). Conclusion: The dose-dependent improvement effect FA supplementation on LPS-induced oxidant/antioxidant balance, inflammatory response and histopathological alterations of lung was shown for the first time. The potential therapeutic intervention of FA in LPS-induced lung damage was highlighted. Keywords: folic acid, LPS, lung, oxidative, inflammation