↓ Skip to main content

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
Altmetric Badge

Citations

dimensions_citation
17 Dimensions

Readers on

mendeley
14 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
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.

Mendeley readers

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%
Pharmacology, Toxicology and Pharmaceutical Science 1 7%
Business, Management and Accounting 1 7%
Other 0 0%
Unknown 3 21%