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Long-term treatment of clarithromycin at a low concentration improves hydrogen peroxide-induced oxidant/antioxidant imbalance in human small airway epithelial cells by increasing Nrf2 mRNA expression

Overview of attention for article published in BMC Pharmacology and Toxicology, February 2017
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Title
Long-term treatment of clarithromycin at a low concentration improves hydrogen peroxide-induced oxidant/antioxidant imbalance in human small airway epithelial cells by increasing Nrf2 mRNA expression
Published in
BMC Pharmacology and Toxicology, February 2017
DOI 10.1186/s40360-017-0119-8
Pubmed ID
Authors

Kuninori Iwayama, Ayuko Kusakabe, Keisuke Ohtsu, Takahiro Nawano, Ryosuke Tatsunami, Ko-ichi Ohtaki, Yoshiko Tampo, Nobumasa Hayase

Abstract

Clarithromycin (CAM), a representative macrolide antibiotic, has been used widely at low doses for long-term therapy of chronic inflammatory airway diseases. Anti-inflammatory effects of macrolide antibiotics were first discovered in clinical practice. Although oxidative stress is known as a key pathogenesis factor in chronic airway inflammatory diseases, the mechanism of action of low-dose, long-term CAM therapy remains unclear. We aimed to examine the cytoprotective action of CAM against hydrogen peroxide (H2O2)-induced cell dysfunction, focusing on CAM dose and treatment duration, and using human small airway epithelial cells (SAECs), the main cells involved in chronic airway inflammatory diseases. SAECs were pretreated with CAM (1, 5 or 10 μM) for 24, 48 or 72 h, and were subsequently exposed to H2O2 for 0.5-4 h. Levels of interleukin (IL)-8, glutathione (GSH) and glutathione disulfide (GSSG), and the activities of nuclear factor (NF)-κB and γ-glutamylcysteine synthetase (γ-GCS) were assayed using specific methods. IL-8 mRNA and NF erythroid 2-related factor 2 (Nrf2) mRNA expression were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). Tukey's multiple comparison test was used for analysis of statistical significance. Pretreatment with low-dose (1 or 5 μM), long-term (72 h) CAM inhibited H2O2-induced IL-8 levels, NF-κB activity, and IL-8 mRNA expression, and improved the GSH/GSSG ratio via the maintenance of γ-GCS expression levels. Similar to its enhancing effect on the GSH/GSSG ratio, pretreatment with low-dose CAM for 72 h significantly increased Nrf2 mRNA expression (p < 0.01 and p < 0.05). In contrast, these alterations were not observed after pretreatment with high-dose (10 μM) or short-term (24 and 48 h) CAM. CAM is efficacious against cell dysfunction caused by oxidative stress under low-dose, long-term treatment conditions. This effect depended on the suppression of NF-κB activation and improvement of the H2O2-induced oxidant/antioxidant imbalance that is achieved by increasing Nrf2 mRNA expression in SAECs. The present study may provide the first evidence of why low-dose, long-term administration of macrolides is effective for treating chronic inflammatory airway diseases.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Other 4 29%
Student > Bachelor 2 14%
Student > Doctoral Student 1 7%
Lecturer 1 7%
Student > Ph. D. Student 1 7%
Other 1 7%
Unknown 4 29%
Readers by discipline Count As %
Medicine and Dentistry 4 29%
Agricultural and Biological Sciences 3 21%
Biochemistry, Genetics and Molecular Biology 2 14%
Business, Management and Accounting 1 7%
Pharmacology, Toxicology and Pharmaceutical Science 1 7%
Other 0 0%
Unknown 3 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 February 2017.
All research outputs
#7,897,686
of 9,110,915 outputs
Outputs from BMC Pharmacology and Toxicology
#193
of 223 outputs
Outputs of similar age
#215,637
of 254,763 outputs
Outputs of similar age from BMC Pharmacology and Toxicology
#4
of 4 outputs
Altmetric has tracked 9,110,915 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 223 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 254,763 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one.