scholarly journals H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation

2016 ◽  
Vol 40 (6) ◽  
pp. 1603-1612 ◽  
Author(s):  
Hong-Xia Zhang ◽  
Shu-Juan Liu ◽  
Xiao-Lu Tang ◽  
Guo-Li Duan ◽  
Xin Ni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Treatment Group ◽  
Lung Injury ◽  
Control Group ◽  
No Production ◽  
Sod Activity ◽  
Nitrative Stress ◽  
Anti Oxidant ◽  
Anti Inflammatory

Background: Hydrogen sulfide (H2S), known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI) induced by endotoxemia. Methods: Male ICR mice were divided in six groups: (1) Control group; (2) GYY4137treatment group; (3) L-NAME treatment group; (4) lipopolysaccharide (LPS) treatment group; (5) LPS with GYY4137 treatment group; and (6) LPS with L-NAME treatment group. The lungs were analysed by histology, NO production in the mouse lungs determined by modified Griess (Sigma-Aldrich) reaction, cytokine levels utilizing commercialkits, and protein abundance by Western blotting. Results: GYY4137, a slowly-releasing H2S donor, improved the histopathological changes in the lungs of endotoxemic mice. Treatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, increased anti-oxidant biomarkers such as thetotal antioxidant capacity (T-AOC) and theactivities of catalase (CAT) and superoxide dismutase (SOD) but decreased a marker of peroxynitrite (ONOO-) action and 3-nitrotyrosine (3-NT) in endotoxemic lung. L-NAME administration also suppressed inflammation in endotoxemic lung, as evidenced by the decreased pulmonary levels of interleukin (IL)-6, IL-8, and myeloperoxidase (MPO) and the increased level of anti-inflammatory cytokine IL-10. GYY4137 treatment reversed endotoxin-induced oxidative/nitrative stress, as evidenced by a decrease in malondialdehyde (MDA), hydrogenperoxide (H2O2) and 3-NT and an increase in the antioxidant biomarker ratio of reduced/oxidized glutathione(GSH/GSSG ratio) and T-AOC, CAT and SOD activity. GYY4137 also attenuated endotoxin-induced lung inflammation. Moreover, treatment with GYY4137 inhibited inducible NOS (iNOS) expression and nitric oxide (NO) production in the endotoxemia lung. Conclusions: GYY4137 conferred protection against acute endotoxemia-associated lung injury, which may have beendue to the anti-oxidant, anti-nitrative and anti-inflammatory properties of GYY4137. The present findings warrant further exploration of the clinical applicability of H2S in the prevention and treatment of ALI.

scholarly journals Immunomodulatory Effect of Chinese Herbal Medicine Formula Sheng-Fei-Yu-Chuan-Tang in Lipopolysaccharide-Induced Acute Lung Injury Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chia-Hung Lin ◽  
Ching-Hua Yeh ◽  
Li-Jen Lin ◽  
Shulhn-Der Wang ◽  
Jen-Shu Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Reactive Oxygen Species Generation ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
No Production ◽  
Anti Inflammatory

Traditional Chinese medicine formula Sheng-Fei-Yu-Chuan-Tang (SFYCT), consisting of 13 medicinal plants, was used to treat patients with lung diseases. This study investigated the immunoregulatory effect of SFYCT on intratracheal lipopolysaccharides- (LPS-) challenged acute lung injury (ALI) mice. SFYCT attenuated pulmonary edema, macrophages, and neutrophils infiltration in the airways. SFYCT decreased inflammatory cytokines, including tumor necrosis factor-α(TNFα), interleukin-1β, and interleukin-6 and inhibited nitric oxide (NO) production but increased anti-inflammatory cytokines, interleukin-4, and interleukin-10, in the bronchoalveolar lavage fluid of LPS-challenged mice. TNFαand monocyte chemotactic protein-1 mRNA expression in the lung of LPS-challenged mice as well as LPS-stimulated lung epithelial cell and macrophage were decreased by SFYCT treatment. SFYCT treatment also decreased the inducible nitric oxide synthase expression and phosphorylation of nuclear factor-κB (NF-κB) in the lung of mice and macrophage with LPS stimulation. SFYCT treatment dose dependently decreased the LPS-induced NO and reactive oxygen species generation in LPS-stimulated macrophage. In conclusion, SFYCT attenuated lung inflammation during LPS-induced ALI through decreasing inflammatory cytokines production while increasing anti-inflammatory cytokines production. The immunoregulatory effect of SFYCT is related to inhibiting NF-κB phosphorylation.

scholarly journals Anti-Inflammatory Effects of Huberia peruviana Cogn. Methanol Extract by Inhibiting Src Activity in the NF-κB Pathway

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2335
Author(s):  
Seung A Kim ◽  
Chae Young Lee ◽  
Ankita Mitra ◽  
Haeyeop Kim ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blotting ◽  
Methanol Extract ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
No Production ◽  
In Vivo Models ◽  
Anti Inflammatory ◽  
Inflammatory Effect

There is a growing need to develop anti-inflammatory drugs to regulate inflammatory responses. An extract of Huberia peruviana Cogn. had the best inhibitory effect on nitric oxide (NO) production in screening process undertaken in our laboratory. However, the anti-inflammatory effect of Huberia peruviana Cogn. methanol extract (Hp-ME) has not been studied. In this study, the anti-inflammatory effect of Hp-ME was assessed by using an NO assay, RT-PCR, luciferase reporter gene activity assay, western blotting assay, HCl/EtOH-induced acute gastritis model, and LPS-induced acute lung injury model. The phytochemical components of Hp-ME were determined through LC-MS/MS analysis. When RAW264.7 and HEK293T cells were treated with Hp-ME, NO production was decreased dose-dependently without cytotoxicity and the mRNA levels of iNOS, COX-2, and TNF-α were decreased. In a luciferase assay, the activity of transcription factors, NF-κB in TRIF or MyD88-overexpressing HEK293T cells was extremely reduced by Hp-ME. The western blotting analysis indicated that Hp-ME has anti-inflammatory effects by inhibiting the phosphorylation of Src. Hp-ME showed anti-inflammatory effects on in vivo models of HCl/EtOH-induced gastritis and LPS-induced acute lung injury. LC-MS/MS revealed that Hp-ME contains several anti-inflammatory flavonoids. The final findings of this study imply that Hp-ME could be used as an anti-inflammatory drug in several inflammatory diseases.

Exhalation of gaseous nitric oxide by rats in response to endotoxin and its absorption by the lungs

1997 ◽  
Vol 82 (1) ◽  
pp. 305-316 ◽  
Author(s):  
John T. Stitt ◽  
Arthur B. Dubois ◽  
James S. Douglas ◽  
Steven G. Shimada
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
No Synthase ◽  
No Production ◽  
Alveolar Air ◽  
Lipopolysaccharide Endotoxin ◽  
Early Biomarker ◽  
Dose Dependent ◽  
Expired Air

Stitt, John T., Arthur B. DuBois, James S. Douglas, and Steven G. Shimada. Exhalation of gaseous nitric oxide by rats in response to endotoxin and its absorption by the lungs. J. Appl. Physiol. 82(1): 305–316, 1997.—Rats injected with a lipopolysaccharide endotoxin produce detectable concentrations of nitric oxide gas (NO) in the expired air within 60 min. The concentration of NO reaches a plateau at 3 h. Production of the NO is dose dependent on lipopolysaccharide, and at a dose of 1 mg/kg iv, lipopolysaccharide alveolar concentrations of >260 parts per billion are observed. NO synthase inhibitors suppress this NO production in response to endotoxin. Experiments were conducted to ascertain the site of origin of this NO and to measure the capacity of the lungs to absorb NO from alveolar air. Results indicate that the endotoxin-induced NO originates from within the lungs themselves and that the lungs have the capacity to absorb >60% of NO that is presented to them. Lung tissues absorb ∼44–47% of the NO load, blood carries away between 15 and 19%, while the remainder is exhaled in the expired air. It is proposed that the exhalation of NO might prove useful as an early biomarker for acute lung injury.

Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats

1999 ◽  
Vol 276 (2) ◽  
pp. L263-L268 ◽  
Author(s):  
Wilhelm S. Cruz ◽  
John A. Corbett ◽  
William J. Longmore ◽  
Michael A. Moxley
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Ex Vivo ◽  
Neutrophil Infiltration ◽  
Inos Expression ◽  
Polymorphonuclear Neutrophil ◽  
No Production ◽  
Biochemical Mechanisms ◽  
Ex Vivo Culture

In this study, the biochemical mechanisms by which N-nitroso- N-methylurethane (NNMU) induces acute lung injury are examined. Polymorphonuclear neutrophil infiltration into the lungs first appears in the bronchoalveolar lavage (BAL) fluid 24 h after NNMU injection (10.58 ± 3.00% of total cells; P < 0.05 vs. control animals). However, NNMU-induced elevation of the alveolar-arterial O2 difference requires 72 h to develop. Daily intraperitoneal injections of the inducible nitric oxide (⋅ NO) synthase (iNOS)-selective inhibitor aminoguanidine (AG) initiated 24 h after NNMU administration improve the survival of NNMU-treated animals. However, AG administration initiated 48 or 72 h after NNMU injection does not significantly improve the survival of NNMU-treated animals. These results suggest that ⋅ NO participates in events that occur early in NNMU-induced acute lung injury. BAL cells isolated from rats 24 and 48 h after NNMU injection produce elevated ⋅ NO and express iNOS during a 24-h ex vivo culture. AG attenuates ⋅ NO production but does not affect iNOS expression, whereas actinomycin D prevents iNOS expression and attenuates ⋅ NO production by BAL cells during this ex vivo culture. These results suggest that NNMU-derived BAL cells can stimulate iNOS expression and ⋅ NO production during culture. In 48-h NNMU-exposed rats, iNOS expression is elevated in homogenates of whole lavaged lungs but not in BAL cells derived from the same lung. These findings suggest that the pathogenic mechanism by which NNMU induces acute lung injury involves BAL cell stimulation of iNOS expression and ⋅ NO production in lung tissue.

scholarly journals Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Peng Tu ◽  
Rong Tian ◽  
Yan Lu ◽  
Yunyi Zhang ◽  
Haiyan Zhu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Influenza A Virus ◽  
Lung Tissue ◽  
Influenza A ◽  
Influenza Viruses ◽  
No Production ◽  
Indigo Naturalis ◽  
Anti Inflammatory

Abstract Background Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI induced by influenza A virus (IAV) in mice. Method The anti-influenza and anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg/kg/day) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA. Result INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05). Conclusion The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.

scholarly journals Deficiency of cationic amino acid transporter-2 protects mice from hyperoxia-induced lung injury

2019 ◽  
Vol 316 (4) ◽  
pp. L598-L607 ◽  
Author(s):  
Yi Jin ◽  
Yusen Liu ◽  
Leif D. Nelin
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Amino Acid ◽  
Lung Injury ◽  
Weight Ratio ◽  
No Production ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Cationic Amino Acid ◽  
Significant Difference

The pathology of acute lung injury (ALI) involves inducible nitric oxide (NO) synthase (iNOS)-derived NO-induced apoptosis of pulmonary endothelial cells. In vitro, iNOS-derived NO production has been shown to depend on the uptake of l-arginine by the cationic amino acid transporters (CAT). To test the hypothesis that mice deficient in CAT-2 ( slc7a2−/− on a C57BL/6 background) would be protected from hyperoxia-induced ALI, mice ( slc7a2−/− or wild-type) were placed in >95% oxygen (hyperoxia) or 21% oxygen (control) for 60 h. In wild-type mice exposed to hyperoxia, the exhaled nitric oxide (exNO) was twofold greater than in wild-type mice exposed to normoxia ( P < 0.005), whereas in slc7a2−/− mice there was no significant difference between exNO in animals exposed to hyperoxia or normoxia ( P = 0.95). Hyperoxia-exposed wild-type mice had greater ( P < 0.05) lung resistance and a lower ( P < 0.05) lung compliance than did hyperoxia-exposed slc7a2−/− mice. The lung wet-to-dry weight ratio was greater ( P < 0.005) in the hyperoxia-exposed wild-type mice than in hyperoxia-exposed slc7a2−/− mice. Neutrophil infiltration was lower ( P < 0.05) in the hyperoxia-exposed slc7a2−/− mice than in the hyperoxia-exposed wild-type mice as measured by myeloperoxidase activity. The protein concentration in bronchoalveolar lavage fluid was lower ( P < 0.001) in the hyperoxia-exposed slc7a2−/− mice than in similarly exposed wild-type mice. The percent of TUNEL-positive cells in the lung following hyperoxia exposure was significantly lower ( P < 0.001) in the slc7a2−/− mice than in the wild-type mice. These results are consistent with our hypothesis that lack of CAT-2 protects mice from acute lung injury.

scholarly journals Beneficial effect of indigo naturalis on acute lung injury induced by influenza A virus

2020 ◽  
Author(s):  
Peng Tu ◽  
Rong Tian ◽  
Yan Lu ◽  
Yunyi Zhang ◽  
Haiyan Zhu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Influenza A Virus ◽  
Lung Tissue ◽  
Influenza A ◽  
Influenza Viruses ◽  
No Production ◽  
Indigo Naturalis ◽  
Anti Inflammatory

Abstract Background: Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of indigo naturalis on ALI induced by influenza A virus (IAV) in mice.Method: The anti-influenza and anti-inflammatory properties of aqueous extract of indigo naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg·kg-1/d) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA.Result: INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05).Conclusion: The results showed that INae alleviated IAV induced ALI in mice. The effect of INAE might be related with its anti-influenza, anti-inflammatory and anti-oxidation properties, which give a hint that indigo naturalis might be effective on respiratory viruses infected acute lung injury or SAR-CoV-2 caused COVID-19.

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