8-hydroxy-2--deoxyguanosine and Acute-Lung-Injury

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are serious clinical complications with a high frequency of morbidity and mortality. The initiation and amplification of inflammation is a well-known aspect in the pathogenesis of ALI and related disorders. Therefore, inhibition of the inflammatory mediators could be an ideal approach to prevent ALI. Epigallocatechin-3-gallate (EGCG), a major constituent of green tea, has been shown to have protective effects on oxidative damage and anti-inflammation. The goal of the present study was to determine whether EGCG improves phenotype and macrophage polarisation in LPS-induced ALI. C57BL/6 mice were given two doses of EGCG (15 mg/kg) intraperitoneally (IP) 1 h before and 3 h after LPS instillation (2 mg/kg). EGCG treatment improved histopathological lesions, Total Leucocyte count (TLC), neutrophils infiltration, wet/dry ratio, total proteins and myeloperoxidase (MPO) activity in LPS-induced lung injury. The results displayed that EGCG reduced LPS-induced ALI as it modulates macrophage polarisation towards M2 status. Furthermore, EGCG also reduced the expression of proinflammatory M1 mediators iNOS TNF-α, IL-1β and IL-6 in the LPS administered lung microenvironment. In addition, it increased the expression of KLF4, Arg1 and ym1, known to augment the M2 phenotype of macrophages. EGCG also alleviated the expression of 8-OHdG, nitrotyrosine, showing its ability to inhibit oxidative damage. TREM1 in the lung tissue and improved lung regenerative capacity by enhancing Ki67, PCNA and Ang-1 protein expression. Together, these results proposed the protective properties of EGCG against LPS-induced ALI in may be attributed to the suppression of M1/M2 macrophages subtype ratio, KLF4 augmentation, lung cell regeneration and regulating oxidative damage in the LPS-induced murine ALI.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Arginase; beta-N-Acetylhexosaminidases; Catechin; Cell Proliferation; Interleukin-1beta; Interleukin-6; Ki-67 Antigen; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lectins; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Peroxidase; Proliferating Cell Nuclear Antigen; Tea; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha; Tyrosine

Simvastatin, which is primarily prescribed to lower cholesterol, may also mitigate lung injury caused by sepsis, although the mechanisms remain elusive. This study aimed to evaluate the protective effect of simvastatin on acute lung injury in rats with sepsis and to investigate possible mechanisms. Male Wistar rats were pretreated with simvastatin (0.2 μg/g) for 1 week before cecal ligation and puncture. Treatment with simvastatin demonstrated significant decreases in the concentration of protein, TNF-α, IL-1β, IL-6, and lipocalin 2, and the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid in septic rats. In addition, simvastatin also reduced levels of Evans blue, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and wet/dry lung weight ratios, and increased the activity of superoxide dismutase in lung tissue. Furthermore, expression levels of TLR4, NF-κB p65, and active caspase-3 proteins and Bax mRNA were also decreased by simvastatin. H&E staining showed that severe lung injury occurred in the sepsis group and that lung injury was reduced by treatment with simvastatin. In conclusion, simvastatin improved endothelial permeability and mitigated the inflammatory response of lung tissue, the oxidative stress response, and cell apoptosis by inhibiting the TLR4/NF-κB signaling pathway, thereby alleviating sepsis-induced acute lung injury in rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Bronchoalveolar Lavage Fluid; Caspase 3; Cytokines; Cytoprotection; Deoxyguanosine; Disease Models, Animal; Inflammation Mediators; Lipocalin-2; Lung; Male; Malondialdehyde; Oxidative Stress; Pulmonary Edema; Rats, Wistar; Sepsis; Signal Transduction; Simvastatin; Superoxide Dismutase; Toll-Like Receptor 4; Transcription Factor RelA

Acute lung injury (ALI) is an inflammatory disorder. Semen Cassiae has potent anti-inflammatory activities. The aim of our study was to investigate whether Semen Cassiae plays a protective effect on lipopolysaccharide (LPS)-induced ALI and, if so, to elucidate its potential mechanism.. Male Sprague-Dawley rat lungs were injured by intratracheal instillation of LPS. Rats were treated with Semen Cassiae or vehicle 3 h after LPS challenge. Samples were harvested 24 h post-LPS administration. We also investigated the effects of Semen Cassiae on LPS stimulation in RAW 264.7 cells.. LPS administration markedly induced pulmonary edema and polymorphonuclear neutrophil influxes. These changes were significantly attenuated in Semen Cassiae treated group. Moreover, Semen Cassiae markedly reduced pulmonary interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The pulmonary soluble epoxide hydrolase (sEH) activity and the DNA binding activity of Nuclear factor (NF)-κB were significantly inhibited in Semen Cassiae treated group. Furthermore, Semen Cassiae treatment significantly increased epoxyeicosatrienoic acids (EETs), and heme oxygenase-1 (HO-1) activity. Our in vitro study demonstrates that Semen Cassiae treatment may inhibit LPS induced IκBα phosphorylation and NF-κB p65 nucleus translocation.. Semen Cassiae protects LPS-induced ALI in rats. Semen Cassiae can be developed as a novel treatment for ALI.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cassia; Cytokines; Deoxyguanosine; Disease Models, Animal; Epoxide Hydrolases; Heme Oxygenase-1; Lipopolysaccharides; Lung; Male; Mice; Neutrophils; NF-kappa B; NF-KappaB Inhibitor alpha; Phytotherapy; Plant Extracts; Pulmonary Edema; Rats, Sprague-Dawley; RAW 264.7 Cells; Seeds

Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Lung Injury; Animals; Aquaporin 5; Bilirubin; Biliverdine; Deoxyguanosine; Gene Expression Regulation; Inflammation Mediators; Lung; Male; Neutrophils; Nitric Oxide Synthase Type II; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Resuscitation; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha

Protective effects of saturated hydrogen (H(2)) saline on cardiac ischaemia-reperfusion (I/R) injury have been demonstrated previously. This study was designed to show that hydrogen-rich saline is protective in preventing lung I/R injury in rats.. Adult male Sprague-Dawley rats underwent 45 min occlusion of the right lung roots and 120 min reperfusion. Rats were divided randomly into three groups: sham-operated control group, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment (0.6 mmol/L, 0.5 ml/kg/d). Three days of intraperitoneal injection of hydrogen-rich saline before the reperfusion combined with immediate administration of hydrogen-rich saline after the reperfusion were performed. Following reperfusion, the lung tissue and the pulmonary artery was immediately obtained and the W/D ratio, pulmonary artery contraction and relaxation ability, H-E staining, TUNEL staining, caspase-3, MDA, 8-OHdG content and measurement of such biomarkers as WBC, CRP were measured or carried out.. Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL.. It is concluded that hydrogen-rich saline is a novel, simple, safe and effective method to attenuate pulmonary I/R injury.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Lung Injury; Animals; Biomarkers; Deoxyguanosine; Hydrogen; Male; Malondialdehyde; Pulmonary Artery; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Respiratory Mucosa; Sodium Chloride