Heme oxygenase-1 mediates the anti-inflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages

Li, Qifang; Zhu, Yu; Jiang, Hong; Xu, Hui; Sun, Yinghao

doi:10.1038/aps.2008.19

Cited by 41 publications

(26 citation statements)

References 24 publications

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“…In the present study, IL-1ß, IL-10 and TNF-α levels significantly increased in the serum of the CLP group when compared to the sham group. These results are in accordance with previous studies [7,42,43] . However, PH1 and PH2 treated CLP groups decreased the cytokine (IL-1ß, IL-10 and TNF-α) levels when compared to the CLP group.…”

Section: Discussionsupporting

confidence: 83%

Peganum harmala Ekstraktının Ratlarda Çekal Bağlama ve Delme ile İndüklenen Sepsiste Akciğer ve Böbrek Üzerine Koruyucu Etkileri

Özkanlar¹,

Koç²,

Karakuş³

et al. 2015

Kafkas Univ Vet Fak Derg

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Sepsis is characterized by multiple organ dysfunction, tissue damage and hyper-inflammation. Peganum harmala (PH) is a plant considered for its antibacterial, antioxidant, anticarcinogen and antiinflammatory properties. This study was aimed to evaluate the protective effects of PH extract on tissues and cytokines in sepsis induced by cecal ligation and perforation (CLP) in rats. Forty rats were divided into five groups. Groups were sham-operated (control), CLP, 90 mg/kg PH-treated CLP, 180 mg/kg PH-treated CLP and 180 mg/kg PH-treated control healthy. Animals were sacrificed at the 16th h of the study. Biochemical and histopathological analyses were performed in lung, kidney and blood samples. Both 90 mg/kg and 180 mg/kg doses of PH decreased the level of interleukin-1 beta (IL-1β) and interleukin-10 (IL-10), and high dose of PH reduced the tumor necrosis factor-alpha (TNF-α) in the serum compared to CLP group. The PH also increased the activity of superoxide dismutase (SOD) and the total levels of glutathione (GSH) in the lung and kidney tissues of septic rats. The level of malondialdehyde (MDA) in the lung and kidney tissues was reduced in both PH treated CLP groups. The histopathological results were in accordance with the biochemical results. The CLP + 180 mg/kg PH group had the lowest inflammation score in the lung. In conclusion, the administration of PH has prevented the oxidative stress, the cytokine response and the inflammation in CLP-induced septic rats. Keywords: Inflammation, polymicrobial sepsis, oxidative stress, cytokine, tissue damage Peganum harmala Ekstraktının Ratlarda Çekal Bağlama ve Delme ile İndüklenen Sepsiste Akciğer ve Böbrek Üzerine Koruyucu Etkileri ÖzetSepsis organlarda fonksiyon bozukluğu, doku hasarı ve hiper-inflamasyon ile karakterizedir. Peganum harmala (PH) antibakteriyel, antioksidant, antikarsinojenik ve antiinflamatuar özellikleri olduğu kabul edilen bir bitkidir. Bu çalışma çekal bağlama ve delme (CLP) ile sepsis oluşturulan ratlarda PH ekstraktının dokular ve sitokinler üzerine koruyucu etkilerinin değerlendirilmesi amacıyla yapılmıştır. Kırk rat 5 gruba ayrıldı. Gruplar sham-operasyon (kontrol) CLP, 90 mg/kg PH-uygulanan CLP, 180 mg/kg PH-uygulanan CLP ve 180 mg/kg PH-uygulanan sağlıklı kontroldür. Hayvanlar çalışmanın 16. saatinde sakrifiye edildi. Akciğer, böbrek ve kan örneklerinde biyokimyasal ve histopatolojik analizler yapıldı. CLP grubuna kıyasla PH'nın 90 mg/kg ve 180 mg/kg her iki dozu da serum interlökin-1 beta (IL1β) ve interlökin-10 (IL-10) düzeylerini azalttı ve yüksek doz PH tümör nekrozis faktör-alfa (TNF-α) düzeyini düşürdü. PH uygulaması septik ratların akciğer ve böbrek dokularındaki süperoksit dismutaz (SOD) aktivitesini ve total glutatyon (GSH) düzeyini de arttırdı. Akciğer ve böbrek dokularındaki malondialdehit (MDA) düzeyi PH uygulanan CLP gruplarında azaldı. Histopatolojik bulgular biyokimyasal bulgular ile uyumluydu. CLP grupları içerisinde, CLP + 180 mg/kg PH grubu akciğerde en düşük inflamasyon skoruna sahipti. Sonuç olarak, PH uygulamas...

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Section: Discussionsupporting

confidence: 83%

Peganum harmala Ekstraktının Ratlarda Çekal Bağlama ve Delme ile İndüklenen Sepsiste Akciğer ve Böbrek Üzerine Koruyucu Etkileri

Özkanlar¹,

Koç²,

Karakuş³

et al. 2015

Kafkas Univ Vet Fak Derg

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“…The anti-inflammatory properties of HO-1 are due to the direct inhibition of adhesion molecule expression and monocyte chemotactic protein 1 and macrophage colonystimulating factor secretion by endothelial cells (24). Moreover, increased HO-1 expression can inhibit the release of proinflammatory mediators, such as TNF and interleukin 6, and the induction of iNOS by lipopolysaccharide-stimulated macrophages (25). Likewise, HO blockade partially inhibited the CLP-induced neutrophil paralysis and, consequently, reduced the mortality rate in mice (13).…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase Inhibition Enhances Neutrophil Migration Into the Bronchoalveolar Spaces and Improves the Outcome of Murine Pneumonia-Induced Sepsis

Czaikoski

Nascimento²,

Sônego³

et al. 2013

Shock

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A reduction of the neutrophil migration into the site of infection during cecal ligation and puncture-induced sepsis increases host mortality. Inhibition of heme oxygenase (HO) prevents this neutrophil paralysis and improves host survival in the cecal ligation and puncture model. Taking into account that almost 50% of all sepsis cases are a consequence of pneumonia, we designed the present study to determine the role of HO in an experimental model of pneumonia-induced sepsis. The objective of this study was to evaluate whether the inhibition of HO improves the outcome and pathophysiologic changes of sepsis induced by an intratracheal instillation of Klebsiella pneumoniae. The pretreatment of mice subjected to pneumonia-induced sepsis with ZnDPBG (zinc deuteroporphyrin 2,4-bis glycol), a nonspecific HO inhibitor, increased the number of neutrophils in the bronchoalveolar spaces, reduced the bacterial load at the site of infection, and prevented the upregulation of CD11b and the downregulation of CXCR2 on blood neutrophils. Moreover, the pretreatment with ZnDPBG decreased alveolar collapse, attenuating the deleterious changes in pulmonary mechanics and gas exchanges and, as a consequence, improved the survival rate of mice from 0% to ∼20%. These results show that heme oxygenase is involved in the pathophysiology of pneumonia-induced sepsis and suggest that HO inhibitors could be helpful for the management of this disease.

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“…Growing evidence indicates that isoflurane, in addition to having anesthetic features, also has anti-inflammatory properties, decreasing cytokine release from alveolar macrophages and monocytes [7][8][9]. The preconditioning properties of isoflurane, which contribute to lung tissue protection, have been described in our previous work [10,11]. In rat lungs, pretreatment with isoflurane protects the vascular endothelium associated with lipopolysaccharide (LPS)-induced inflammation and diminishes LPS-induced lung edema and vascular permeability.…”

Section: Introductionmentioning

confidence: 90%

Isoflurane post-treatment improves pulmonary vascular permeability via upregulation of heme oxygenase-1

Dong¹,

Hu²,

Sun³

et al. 2013

Experimental Lung Research

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Isoflurane (ISO) has been shown to attenuate acute lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular injury. The aim of this study was to investigate the effect of post-treatment with isoflurane on lung vascular permeability and the role of HO-1 in an ALI rat model induced by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned to one of four groups: sham group, sham rats post-treated with vehicle (Sham); CLP group, CLP rats post-treated with vehicle (CLP); ISO group, CLP rats post-treated with isoflurane (ISO); and ZnPP group, CLP rats injected with zinc protoporphyrin IX (ZnPP), a competitive inhibitor of HO-1, 1 hour before the operation, and post-treated with isoflurane (ZnPP). Isoflurane (1.4%) was administered 2 hour after CLP. At 24 hour after CLP, the extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye (EBD) extravasation, lung permeability index (LPI), as well as histological and immunohistochemical examinations. We also determined pulmonary iNOS and HO-1 expression. Compared with the CLP group, the isoflurane post-treatment group showed improved pulmonary microvascular permeability as detected by EBD extravasation, LPI, as well as histological and immunohistochemical examinations. Furthermore, isoflurane decreased iNOS and increased HO-1 expression in lung tissue. Pretreatment with ZnPP prevented the protective effects of isoflurane in rats. These findings indicate that the protective role of isoflurane post-conditioning against CLP-induced lung injury may be associated with its role in upregulating HO-1 in ALI.

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Heme oxygenase-1 mediates the anti-inflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages

Cited by 41 publications

References 24 publications

Peganum harmala Ekstraktının Ratlarda Çekal Bağlama ve Delme ile İndüklenen Sepsiste Akciğer ve Böbrek Üzerine Koruyucu Etkileri

Peganum harmala Ekstraktının Ratlarda Çekal Bağlama ve Delme ile İndüklenen Sepsiste Akciğer ve Böbrek Üzerine Koruyucu Etkileri

Heme Oxygenase Inhibition Enhances Neutrophil Migration Into the Bronchoalveolar Spaces and Improves the Outcome of Murine Pneumonia-Induced Sepsis

Isoflurane post-treatment improves pulmonary vascular permeability via upregulation of heme oxygenase-1

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