Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression

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Abstract

Background

Intestinal mucosa barrier dysfunction after burn injury is an important factor for causing mortality of burn patients. The current study established a burn model in rats and used a free radical scavenger edaravone (ED) to treat the rats, so as to investigate the effect of edaravone on intestinal mucosa barrier after burn injury.

Methods

Anesthetized rats were subjected to 40% total body surface area water burn immediately, followed by treatment with ED, scrambled antagomir, or antagomiR-320. Intestinal mucosa damage was observed by hematoxylin-eosin staining and graded by colon mucosal damage index (CMDI) score. The contents of total sulfhydryl (TSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were determined by spectrophotometry. Cell apoptosis, protein relative expression,and the in situ expressions of p-Akt and p-Bad were detected by flow cytometry, Western blotting and immunohistochemistry, respectively. The miR-320 expression was determined by quantitative real-time polymerase chain reaction.

Results

ED alleviated intestinal mucosal damage caused by burn injury, down-regulated the levels of MDA, cytochrome C, cleaved caspase-9 and cleaved caspase-3, but up-regulated the levels of TSH, SOD, CAT and Bcl-2. We also found that ED could reduce oxidative stress, inhibit cell apoptosis, increase the expressions of p-Akt, p-Bad and miR-320, and decrease PTEN expression. PTEN was predicted to be the target gene for miR-320, and cell apoptosis could be promoted by inhibiting miR-320 expression.

Conclusion

ED regulates Akt/Bad/Caspase signaling cascade to reduce apoptosis and oxidative stress through up-regulating miR-320 expression and down-regulating PTEN expression, thus protecting the intestinal mucosal barrier of rats from burn injury.

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Most cited references 35

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Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation

Zachary M. Earley, Suhail Akhtar, Stefan Green … (2015)

Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.

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miR-494-3p Regulates Cellular Proliferation, Invasion, Migration, and Apoptosis by PTEN/AKT Signaling in Human Glioblastoma Cells

Xue-tao Li, Hang-zhou Wang, Zhi-wu Wu … (2015)

Malignant gliomas are the most common primary brain tumors, and the molecular mechanisms involving their progression and recurrence are still largely unclear. Substantial data indicate that the oncogene miR-494-3p is significantly elevated in gliomas, but the molecular functions of miR-494-3p in gliomagenesis are largely unknown. The present study aimed to explore the role of miR-494-3p and its molecular mechanism in human brain gliomas, malignant glioma cell lines, and cancer stem-like cells. The expression level of miR-494-3p in 48 human glioma issues and 8 normal brain tissues was determined using stem-loop real-time polymerase chain reaction (PCR). To study the function of miR-494-3p inhibitor in glioma cells, the miR-494-3p inhibitor lentivirus was used to transfect glioma cells. Transwell invasion system was used to estimate the effects of miR-494-3p inhibitor on the invasiveness of glioma cells. A mouse model was used to test the effect of miR-494-3p inhibitor on glioma proliferation and invasion in vivo. Results showed that the expression of miR-494-3p in human brain glioma tissues was higher than in normal brain tissues. Downregulated expression of miR-494-3p can inhibit the invasion and proliferation and promote apoptosis in glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that the expression of PTEN was increased after downexpression of miR-494-3p in glioma cells (U87 and U251). miR-494-3p inhibitor could prevent migration, invasion, proliferation, and promote apotosis in gliomas through PTEN/AKT pathway. Therefore, the study results have shown that miR-494-3p may act as a therapeutic target in gliomas.

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Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

Fereshteh Ahmadinejad, Simon Geir Møller, Morteza Hashemzadeh-Chaleshtori … (2017)

Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinson’s disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1). Although they share the targets in reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis.

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Author and article information

Contributors

Jiaxiang Ke: jiayang_ke@163.com

Xi Bian: bianxi_xb@163.com

Hu Liu: liuhu_hul@163.com

Bei Li: liebei_beil@163.com

Ran Huo:

ORCID: http://orcid.org/0000-0002-3849-5569

huoran_ranh@163.com

Journal

Journal ID (nlm-ta): Mol Med

Journal ID (iso-abbrev): Mol. Med

Title: Molecular Medicine

Publisher: BioMed Central (London )

ISSN (Print): 1076-1551

ISSN (Electronic): 1528-3658

Publication date (Electronic): 11 December 2019

Publication date PMC-release: 11 December 2019

Publication date Collection: 2019

Volume: 25

Electronic Location Identifier: 54

Affiliations

[1 ]ISNI 0000 0004 1761 1174, GRID grid.27255.37, Burn and Plastic Section, Qingdao Municipal Hospital Affiliated to Shandong University, ; Qingdao, China

[2 ]ISNI 0000 0004 1761 1174, GRID grid.27255.37, Burn and Plastic Section, Shandong Province Hospital Affiliated to Shandong University, ; Jiaozhou Road, Shibei District, Qingdao, 266011 Shandong Province China

Author information

Ran Huo http://orcid.org/0000-0002-3849-5569

Article

Publisher ID: 122

DOI: 10.1186/s10020-019-0122-1

PMC ID: 6907153

PubMed ID: 31829167

SO-VID: 8751a433-8830-4814-a491-75aeb93e916d

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 23 July 2019

Date accepted : 21 November 2019

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Keywords: edaravone,oxidative stress,apoptosis,mir-320,intestinal mucosa damage

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Keywords: edaravone, oxidative stress, apoptosis, mir-320, intestinal mucosa damage

Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression

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Most cited references 35

Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation

miR-494-3p Regulates Cellular Proliferation, Invasion, Migration, and Apoptosis by PTEN/AKT Signaling in Human Glioblastoma Cells

Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

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