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

Abstract

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.

The effect of vitamin D, magnesium and zinc supplements on interferon signaling pathways and their relationship to control SARS-CoV-2 infection

“…In addition to TIM-3, the activation of the PD-1/PD-L1 pathway in severe H1N1 influenza A infection has been demonstrated in tissue samples of the lower respiratory tract in pediatric patients and their dendritic and T cells as well [21,22]. PD-L1 expression levels are inversely related to the number of CD8 + T cells in these patients, and inhibition of this pathway improves the number and function of CD8 + T cells [23]. Rutigliano et al showed that decreased CD8 + T cells activity in influenza A virus infection in mice was associated with increased PD-1 expression [24].…”

“…The antiviral activity is attributed to their binding to IFN-receptor and inducing STAT1/2, IRF7, IRF9, and production of ISGF3 as well [22]. Clarithromycin and Leucomycin are the examples of Macrolides, used against the influenza virus to increase IFN-α production [23,38]. Azithromycin is another macrolide that inhibits rhinoviruses via potentiating IFN-I signaling.…”