Valproic Acid Attenuates Acute Lung Injury Induced by Ischemia–Reperfusion in Rats

Wu, Shu-Yu; Tang, Shou-Hung; Ko, Fu-Chang; Wu, Gong-Jhe; Huang, Kunlun; Chu, Shi-Jye

doi:10.1097/aln.0000000000000618

Cited by 59 publications

(71 citation statements)

References 28 publications

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“…The Animal Review Committee of National Defense Medical Center approved the study protocol. Rat lungs were isolated and perfused as previously described [13–15]. Briefly, Sprague-Dawley male rats (350 ± 20 g) were ventilated with humidified air containing 5% CO 2 at a tidal volume of 3 ml, a positive end-expiratory pressure of 1 cm H 2 O, and a rate of 60 breaths/min.…”

Section: Methodsmentioning

confidence: 99%

“…The levels of TNF-α, IL-6 and cytokine-induced neutrophil chemoattractant (CINC)-1 in the BALF were measured using a commercial ELISA kit (R&D Systems Inc., Minneapolis, MN, USA). Total cell counts in the BALF were assessed as described previously [15]. …”

Section: Methodsmentioning

confidence: 99%

“…The malondialdehyde content of the supernatant was measured by absorbance at 532 nm and was expressed as nmol/mg protein. The oxidative damage to the proteins in the lung tissue was assessed by determining the carbonyl group content based on a reaction with dinitrophenylhidrazine as previously described [15]. The carbonyl content was determined from the absorbance at 370 nm assuming a molar absorption coefficient of 220,000 M −1 and was expressed as the concentration of carbonyl derivatives in the protein (nmol carbonyl/mg protein) [15].…”

Section: Methodsmentioning

confidence: 99%

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Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats

Liao

et al. 2017

Respir Res

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BackgroundEmerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats.MethodsIsolated perfused rat lungs were subjected to 40 min of ischemia followed by 60 min of reperfusion. The rats were randomly allotted to the control, control + FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R + FK866 groups (n = 6 per group). The effects of FK866 on human alveolar epithelial cells exposed to hypoxia-reoxygenation (H/R) were also investigated.ResultsTreatment with FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs. Comparably, the in vitro experiments showed that FK866 also inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R.ConclusionsOur findings suggest that NAMPT inhibition may be a novel therapeutic approach for I/R-induced lung injury. The protective effects involve the suppression of multiple signal pathways.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats

Liao

et al. 2017

Respir Res

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“…Patients with longer HMOX1 promoters suffered from more severe injury cause by stress-associated diseases such as myocardial infarction than patients with shorter HMOX1 promoters probably due to the lower HO-1 levels. [13] With respect to the patients with the longer HMOX1 promoters, exogenous HO-1 byproduct supplement maybe is an important means to treat HO-1 associated diseases. Heme-derived byproducts, especially BV, exhibit cytoprotective effects on oxidative stress injury.…”

Section: Introductionmentioning

confidence: 99%

Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects

Tian

Weng

Sheng

et al. 2017

Chinese Medical Journal

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Background:Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI.Methods:Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment.Results:Lungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P < 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P < 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P < 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P < 0.001, and P < 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P < 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-β) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P < 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group).Conclusion:BV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

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“…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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Valproic Acid Attenuates Acute Lung Injury Induced by Ischemia–Reperfusion in Rats

Abstract: VPA protected against I/R-induced lung injury. The protective mechanism may be partly due to enhanced HO-1 activity following HDAC inhibition.

Cited by 59 publications

References 28 publications

Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats

Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats

Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects

Ratlarda Oleik Asit Kaynaklı Akut Akciğer Hasarı Üzerine Rutinin Koruyucu Etkileri

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