Leptin Attenuates Lipopolysaccharide or Oleic Acid-Induced Acute Lung Injury in Mice

Dong, Huijuan; Xu, Min; Ji, Zhenyu; Wang, Yanxia; Dong, Mingqing; Liu, Man-Ling; Xu, Dan; Zhao, Peng-Tao; Liu, Yi; Luo, Ying; Niu, Wen; Zhang, Bo; Ye, Jing; Li, Zhichao

doi:10.1165/rcmb.2012-0301oc

Cited by 12 publications

(13 citation statements)

References 27 publications

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“…In this line, leptin’s actions in non-obese, septic patients has earned increased attention (Tzanela et al, 2006; Koch et al, 2010). Leptin administration to non-obese subjects suffering from sepsis syndrome and endotoxemia improves survival, probably by mediating the activity of the immune response (Madiehe et al, 2003; Dong et al, 2013; Landgraf et al, 2014; Siegl et al, 2014; Negrin et al, 2017). Furthermore, exogenous leptin administration to leptin-deficient mice improved the pulmonary bacterial clearance and survival during pneumococcal pneumonia (Hsu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have shown that the administration of leptin induces protection during sepsis syndrome and endotoxemia by reducing the immune response and other deleterious characteristics (Dong et al, 2013; Landgraf et al, 2014; Negrin et al, 2017). Lipopolysaccharide-induced acute lung injury is lessened by exogenous leptin administration (Dong et al, 2013; Landgraf et al, 2014), and hyperleptinemia generates resistance to endotoxemia (Madiehe et al, 2003), improving sepsis survival and modulating the immune response (Siegl et al, 2014). In the same line, decreased plasma leptin enhances susceptibility to mortality induced by endotoxemia (Faggioni et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Preventive Leptin Administration Protects Against Sepsis Through Improving Hypotension, Tachycardia, Oxidative Stress Burst, Multiple Organ Dysfunction, and Increasing Survival

et al. 2018

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Sepsis syndrome is the most important cause of mortality in critically ill patients admitted to intensive care units (ICUs). However, current therapies for its prevention and treatment are still unsatisfactory, and the mortality rate is still high. Non-septic ICU patients are vulnerable to acquire sepsis syndrome. Thus, a preventive treatment for this population is needed. During sepsis syndrome and endotoxemia, severe hypotension, tachycardia, oxidative and immune response increase, multiple organ dysfunction syndrome (MODS) and decreased survival are observed. Leptin administration protects against negative effects of sepsis syndrome and endotoxemia. Furthermore, it is has been reported that leptin elevates blood pressure mediated by sympathetic nervous system activation. However, whether leptin administration before sepsis induction mediates its protective effects during sepsis through blood pressure regulation is not known. Therefore, we investigated whether pre-treatment of leptin improves blood pressure and MODS, resulting in survival increase during endotoxemia. The results showed that leptin administration before endotoxemia induction reduced both the hypotension and tachycardia characteristically observed during endotoxemia. Notably, this protective effect was observed early and late in the course of endotoxemia. Endotoxemia-induced MODS decreased in leptin-treated rats, which was reflected in normal values for liver and kidney function, inhibition of muscle mass wasting and maintenance of glycemia. Furthermore, leptin pre-treatment decreased the oxidative stress burst in blood and blunted the increased pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 observed during endotoxemia. Remarkably, according to the leptin-induced increase in survival, leptin pre-administration decreased the risk for death associated with sepsis syndrome at early and late times after endotoxemia induction. These results show a potential preventive therapy against sepsis syndrome and endotoxemia in vulnerable patients, based in the beneficial actions of leptin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preventive Leptin Administration Protects Against Sepsis Through Improving Hypotension, Tachycardia, Oxidative Stress Burst, Multiple Organ Dysfunction, and Increasing Survival

et al. 2018

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“…Leptin-deficient mice (ob/ob) seem to be unaffected [14] or protected [15] from the deleterious effects of endotoxin. On the other hand, Gultekin et al [16] demonstrated that exogenous leptin may be protective role in cerulein-induced acute pancreatitis associated to ALI, and Dong et al [17] showed that leptin-deficient ob/ob mice were more susceptible to LPS-related lethality than lean mice. Therefore, the present study was designed to investigate the effects of acute exogenous leptin treatment in the development of LPS-induced acute lung inflammation in mice.…”

Section: Introductionmentioning

confidence: 99%

Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

Landgraf

Silva

Corrêa-Costa

et al. 2014

Cell Physiol Biochem

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Background/Aims: We investigated the effects of leptin in the development of lipopolysaccharide (LPS)-induced acute lung inflammation (ALI) in lean mice. Methods: Mice were administered leptin (1.0µg/g) or leptin (1.0µg/g) followed by LPS (1.5µg/g) intranasally. Additionally, some animals were given LPS (1.5µg/g) or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation. Results: We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL). We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-α, IFN-γ, GM-CSF and VEGF). LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event. Conclusion: These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.

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“…There are many studies where OA is used to form ALI in many species such as rat [25] , mouse [17] , dog [26] and rabbit [27] . Nonenzymatic lipid peroxidation is an important point in the oxidative stress related cellular damage caused by free radicals.…”

Section: Discussionmentioning

confidence: 99%

“…Various methods in order to create experimental ALI types have been developed on laboratory animals. The primary ones of these methods are lipopolysaccharide (LPS) [4] , acid aspiration [14] , surfactant consumption with saline lavage [15] , pulmonary ischemia/ reperfusion [16] , cecal ligation and puncturing [5] and application of oleic acid (OA) [17] . OA applied intravascularly cause damage in pulmonary vascular endothelial cells and inflammation in the lungs [6] .…”

Section: Introductionmentioning

confidence: 99%

Ratlarda Oleik Asit Kaynaklı Akut Akciğer Hasarı Üzerine Rutinin Koruyucu Etkileri

Aktaş¹,

Kandemir²,

Özkaraca³

et al. 2017

Kafkas Univ Vet Fak Derg

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Citation of This ArticleAktaş MS, Kandemir FM, Özkaraca M, Hanedan B, Kırbaş A: Protective effects of rutin on acute lung injury induced by oleic acid in rats. Kafkas Univ Vet Fak Derg, 23 (3): 445-451, 2017445-451, . DOI: 10.9775/kvfd.2016 AbstractThe purpose of this study was to explore the protective effects of different doses of rutin with the antioxidant and anti-inflammatory properties on acute lung injury (ALI) induced by oleic acid (OA) in rats. Thirty-five Sprague-Dawley male rats were randomly separated into five groups comprising control, rutin 150 mg, OA, rutin 75 mg + OA and rutin 150 mg + OA. In the rutin 75 mg + OA and rutin 150 mg + OA groups, the lung malondialdehyde level (MDA) was significantly lower than that of the OA group. In the rutin 75 mg + OA and and rutin 150 mg + OA groups, the lung GPx (glutathione peroxidase), CAT (catalase) and SOD (superoxide dismutase) activities and GSH (glutathione) levels were significantly higher than those of the OA group, and significantly lower than those of the control group. iNOS expressions in the interstitial parts of the lungs were significantly lower than those of the OA group. The iNOS expression was lower in the 150 mg + OA group compared to the rutin 75 mg + OA group. It was concluded that on the ALI induced by OA, rutin had protective effects through the antioxidant and antiinflammatory properties and that the treatment of rutin as a supportive treatment in ALI was found to be practically useful. Keywords: Acute lung injury, Oleic acid, Oxidative stress, Rutin Ratlarda Oleik Asit Kaynaklı Akut Akciğer Hasarı Üzerine Rutinin Koruyucu Etkileri ÖzetBu çalışmanın amacı ratlarda rutinin farklı dozlarının antioksidan ve anti-inflamatuar özellikleri yoluyla oleik asit (OA) ile oluşturulan akut akciğer hasarı (ALI) üzerine koruyucu etkilerini araştırmaktı. 35 adet Sprague-Dawley erkek rat kontrol, rutin 150 mg, OA, rutin 75 mg + OA ve rutin 150 mg + OA olmak üzere rasgele 5 gruba ayrıldı. Rutin 75 mg + OA ve rutin 150 mg + OA gruplarında akciğer malondialdehit (MDA) düzeyi OA grubununkine göre önemli düzeyde düşüktü. Rutin 75 mg + OA ve rutin 150 mg + OA gruplarında akciğer GPx (glutasyon peroksidaz), CAT (katalaz), SOD (süperoksit dismutaz) aktiviteleri ile GSH (glutatyon) düzeyleri OA grubununkilere göre önemli düzeyde yüksekti ve kontrol grubununkilere göre önemli düzeyde düşüktü. Rutin 75 mg + OA ve rutin 150 mg + OA gruplarında akciğerlerin interstisyel kısımlarında iNOS ekspresyonları OA grubunkilere göre önemli düzeyde düşüktü. OA ile oluşturulan ALI'de rutinin antioksidan ve antiinflamatuvar özellikler aracılığıyla koruyucu etkilere sahip olduğu, ALI'de destekleyici tedavi amacıyla rutin uygulamasının pratik olarak yararlı olduğu tespit edildi.

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Leptin Attenuates Lipopolysaccharide or Oleic Acid-Induced Acute Lung Injury in Mice

Cited by 12 publications

References 27 publications

Preventive Leptin Administration Protects Against Sepsis Through Improving Hypotension, Tachycardia, Oxidative Stress Burst, Multiple Organ Dysfunction, and Increasing Survival

Preventive Leptin Administration Protects Against Sepsis Through Improving Hypotension, Tachycardia, Oxidative Stress Burst, Multiple Organ Dysfunction, and Increasing Survival

Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

Ratlarda Oleik Asit Kaynaklı Akut Akciğer Hasarı Üzerine Rutinin Koruyucu Etkileri

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