A novel genetic modifier for clarithromycin-related cardiac arrhythmia risk?

Hancox, Jules C.; Du, Chunyun; Harchi, Aziza El; Baranchuk, Adrián; Zhang, Henggui

doi:10.1177/2049936114522996

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…Han et al found that mutations in drug-binding sites of the hERG channel could attenuate hERG current obstruction by roxithromycin, but did not significantly modify the disruption of trafficking [39]. According to Hancox et al study, D85N KCNE1 mutations demonstrated an increase in the sensitivity of IKr/hERG to inhibition with clarithromycin in vitro models [40].…”

Section: Original Articlementioning

confidence: 99%

Comparative Study of the Effect of Macrolide Antibiotics Erythromycin, Clarithromycin, and Azithromycin on the ERG1 Gene Expression in H9c2 Cardiomyoblast Cells

et al. 2020

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Macrolides are clinically well-established class of antibiotics. Macrolides induce cardiotoxicity by blocking ether-a-go-go–related gene (ERG) potassium channels in cardiac myocytes. The aim of this study was to compare the effects of erythromycin, clarithromycin and azithromycin on cell viability and expression of ERG1 gene in H9c2 cells. Cell viability and ERG1 gene expression of H9c2 cells in 3 different concentrations, 1, 10 and 25 µg/ml, after 48 and 72 h were determined by MTT test and Real time-PCR method respectively. After 48 h, the growth of H9c2 cells treated with erythromycin, clarithromycin and Azithromycin (except two doses) were inhibited significantly compared to control group (p<0.05). All three groups of antibiotics showed toxic effects on cells after 72 h in all concentrations. Azithromycin-inhibiting effects were significantly higher than two other groups after 72 h of treatment. The expression of ERG1 gene increased in all three groups of antibiotics by increasing the concentration and duration of treatment. Azithromycin had the most pronounced effect on ERG1 expression in 48 and 72 h. This study indicated that these macrolides affect ERG1 expression due to their potential cardiac adverse effects. Further investigations are required to understand the exact mechanism of cardiotoxicity associated with macrolides.

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Section: Original Articlementioning

confidence: 99%

Comparative Study of the Effect of Macrolide Antibiotics Erythromycin, Clarithromycin, and Azithromycin on the ERG1 Gene Expression in H9c2 Cardiomyoblast Cells

et al. 2020

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“…According to Hancox et al study, D85N KCNE1 mutations demonstrated an increase in the sensitivity of IKr/hERG to inhibition with clarithromycin in vitro models [51].…”

Section: Macrolides Such As Erythromycin and Clarithromycin May Contrmentioning

confidence: 99%

Comparative Study of the Effect of Macrolide Antibiotics Erythromycin, Clarithromycin, and Azithromycin on the ERG1 Gene Expression in H9c2 Cardiomyoblast Cells

Hajimirzaei

Khalili

Boroumand

et al. 2020

Preprint

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Background: Macrolides are a clinically well-established class of antibiotics. Macrolides induce cardiotoxicity by blocking ERG potassium channels in cardiac myocytes. The aim of this study was to compare the effects of erythromycin, clarithromycin and azithromycin on cell viability and expression of ERG1 gene in H9c2 cells. Methods: Cell viability and ERG1 gene expression of H9c2 cells in 3 different concentrations, 1, 10 and 25µg/ml, after 48 and 72 hours were determined by MTT test and Real time-PCR method respectively. Results: According to the results, these antibiotics decreased cell viability in a concentration and time-dependent manner. After 48 hours, the growth of H9c2 cells treated with erythromycin and clarithromycin (at 1 and 25 μg/ml) were inhibited significantly compared to control group (p <0.05). All three groups of antibiotics showed toxic effects on cells after 72 hours in all concentrations. Azithromycin-inhibiting effects were significantly higher than two other groups after 72 hours of treatment. The expression of ERG1 gene increased in all three groups of antibiotics by increasing the concentration and duration of treatment. Azithromycin had the most pronounced effect on ERG1 expression in 48 and 72 hours. Conclusions: This study indicated that these macrolides affect ERG1 expression due to their potential cardiac adverse effects. Further investigations are required to understand the exact mechanism of cardiotoxicity associated with macrolides.

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