scholarly journals Hydromorphone Protects against CO2 Pneumoperitoneum-Induced Lung Injury via Heme Oxygenase-1-Regulated Mitochondrial Dynamics

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Jia Shi ◽  
Shi-Han Du ◽  
Jian-Bo Yu ◽  
Yan-Fang Zhang ◽  
Si-Meng He ◽  
...  
Keyword(s):  
Lung Injury ◽  
Heme Oxygenase ◽  
Mitochondrial Dynamics ◽  
Stress Index ◽  
Heme Oxygenase 1 ◽  
Mitochondrial Morphology ◽  
Gynecological Surgery ◽  
Protective Effects ◽  
Co2 Pneumoperitoneum ◽  
Blood Samples

Various pharmacological agents and protective methods have been shown to reverse pneumoperitoneum-related lung injury, but identifying the best strategy is challenging. Herein, we employed lung tissues and blood samples from C57BL/6 mice with pneumoperitoneum-induced lung injury and blood samples from patients who received laparoscopic gynecological surgery to investigate the therapeutic role of hydromorphone in pneumoperitoneum-induced lung injury along with the underlying mechanism. We found that pretreatment with hydromorphone alleviated lung injury in mice that underwent CO2 insufflation, decreased the levels of myeloperoxidase (MPO), total oxidant status (TOS), and oxidative stress index (OSI), and increased total antioxidant status (TAS). In addition, after pretreatment with hydromorphone, upregulated HO-1 protein expression, reduced mitochondrial DNA content, and improved mitochondrial morphology and dynamics were observed in mice subjected to pneumoperitoneum. Immunohistochemical staining also verified that hydromorphone could increase the expression of HO-1 in lung tissues in mice subjected to CO2 pneumoperitoneum. Notably, in mice treated with HO-1-siRNA, the protective effects of hydromorphone against pneumoperitoneum-induced lung injury were abolished, and hydromorphone did not have additional protective effects on mitochondria. Additionally, in clinical patients who received laparoscopic gynecological surgery, pretreatment with hydromorphone resulted in lower serum levels of club cell secretory protein-16 (CC-16) and intercellular adhesion molecule-1 (ICAM-1), a lower prooxidant-antioxidant balance (PAB), and higher heme oxygenase-1 (HO-1) activity than morphine pretreatment. Collectively, our results suggest that hydromorphone protects against CO2 pneumoperitoneum-induced lung injury via HO-1-regulated mitochondrial dynamics and may be a promising strategy to treat CO2 pneumoperitoneum-induced lung injury.

Protective Effects of Heme Oxygenase-1 in Acute Lung Injury

CHEST Journal ◽  
1999 ◽  
Vol 116 ◽  
pp. 61S-63S ◽  
Author(s):  
Leo E. Otterbein ◽  
Patty J. Lee ◽  
Beek Yoke Chin ◽  
Irina Petrache ◽  
Sharon L. Camhi ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Protective Effects

AICAR decreases acute lung injury by phosphorylating AMPK and upregulating heme oxygenase-1

2021 ◽  
pp. 2003694
Author(s):  
Israr Ahmad ◽  
Adam Molyvdas ◽  
Ming-Yuan Jian ◽  
Ting Zhou ◽  
Amie M. Traylor ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Protective Action ◽  
High Mobility ◽  
Adenosine Monophosphate ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Post Exposure ◽  
Liver Kinase B1

IntroductionHerein we investigated the mechanisms by which 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of adenosine monophosphate (AMP)-activated protein kinase (AMPK), administered to mice post exposure to bromine (Br2), decreases lung injury and mortality.MethodsWe exposed male C57BL/6 mice as well as heme oxygenase-1 deficient (HO-1−/−) and corresponding WT littermate mice to Br2 (600 ppm for 45 or 30 min respectively) gas in environmental chambers and returned them to room air. AICAR was administered 6 h post-exposure (10 mg·kg−1, IP). We assessed survival, indices of lung injury, high mobility group box 1 (HMGB1) in the plasma, HO-1 levels in lung tissues and phosphorylation of AMPK and its upstream liver kinase B1 (LKB1). Rat lung Type II epithelial cells (L2) and human club-like epithelial cells (H441) were also exposed to Br2 (100 ppm for 10 min). Twenty-four h later we measured apoptosis and necrosis, AMPK and LKB1 phosphorylation and HO-1 expression.ResultsThere was a marked downregulation of phosphorylated AMPK and LKB1 in both lung tissues and L2 and H441 cells post-exposure. AICAR increased survival in C57BL/6 but not in HO-1−/− mice. Additionally, in WT mice AICAR decreased lung injury and restored pAMPK and pLKB1 to control levels and increased HO-1 levels in both lung tissues and cells exposed to Br2. Treatment of L2 and H441 cells with siRNAs against Nrf2 or HO-1 abrogated the protective effects of AICAR.ConclusionsOur data indicate that the primary mechanism for the protective action of AICAR in toxic gas injury is by upregulating lung HO-1 levels.

scholarly journals Pterostilbene 4′-β-Glucoside Attenuates LPS-Induced Acute Lung Injury via Induction of Heme Oxygenase-1

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Jeongmin Park ◽  
Yingqing Chen ◽  
Min Zheng ◽  
Jinhyun Ryu ◽  
Gyeong Jae Cho ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mouse Lung ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Protective Effects ◽  
Anti Inflammatory

Heme oxygenase-1 (HO-1) can exert anti-inflammatory and antioxidant effects. Acute lung injury (ALI) is associated with increased inflammation and influx of proinflammatory cells and mediators in the airspaces and lung parenchyma. In this study, we demonstrate that pterostilbene 4′-β-glucoside (4-PG), the glycosylated form of the antioxidant pterostilbene (PTER), can protect against lipopolysaccharide- (LPS-) orPseudomonas aeruginosa- (P. aeruginosa-) induced ALI when applied as a pretreatment or therapeutic post-treatment, via the induction of HO-1. To determine whether HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG, we subjected mice genetically deficient inHmox-1to LPS-induced ALI and evaluated histological changes, HO-1 expression, and proinflammatory cytokine levels in bronchoalveolar lavage (BAL) fluid. 4-PG exhibited protective effects on LPS- orP. aeruginosa-induced ALI by ameliorating pathological changes in lung tissue and decreasing proinflammatory cytokines. In addition, HO-1 expression was significantly increased by 4-PG in cells and in mouse lung tissues. The glycosylated form of pterostilbene (4-PG) was more effective than PTER in inducing HO-1 expression. Genetic deletion ofHmox-1abolished the protective effects of 4-PG against LPS-induced inflammatory responses. Furthermore, we found that 4-PG decreased both intracellular ROS levels and mitochondrial (mt) ROS production in a manner dependent on HO-1. Pharmacological application of the HO-1 reaction product carbon monoxide (CO), but not biliverdin or iron, conferred protection inHmox-1-deficient macrophages. Taken together, these results demonstrate that 4-PG can increase HO-1 expression, which plays a critical role in ameliorating intracellular and mitochondrial ROS production, as well as in downregulating inflammatory responses induced by LPS. Therefore, these findings strongly suggest that HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG.

Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1

2010 ◽  
Vol 62 (1) ◽  
pp. 170-177 ◽  
Author(s):  
Zhi-Jun Ge ◽  
Guo-Jun Jiang ◽  
Yan-Ping Zhao ◽  
Guo-Xiang Wang ◽  
Yong-Fei Tan
Keyword(s):  
Lung Injury ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

scholarly journals Upregulation of Heme Oxygenase-1 by Hemin Alleviates Sepsis-Induced Muscle Wasting in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiongwei Yu ◽  
Wenjun Han ◽  
Changli Wang ◽  
Daming Sui ◽  
Jinjun Bian ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heme Oxygenase ◽  
Muscle Atrophy ◽  
Muscle Wasting ◽  
Cecal Ligation ◽  
Skeletal Muscle Atrophy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Sod Activity

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.

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