Evaluation of Possible Genotoxic Activity of Dirithromycin in Cultured Human Lymphocytes.

Ahmet Kayraldız,Ayşe Yavuz Kocaman,Şule Gökçe,Lale Dönbak,Esra Köker

doi:10.1155/2015/535490

Ahmet Kayraldız, Ayşe Yavuz Kocaman + Show 3 more

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https://doi.org/10.1155/2015/535490

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Abstract

Dirithromycin antibiotic is a 14-membered lactone ring macrolide and is widely used in medicine to treat many different types of bacterial infections. In the present study, the possible genotoxicity of dirithromycin was evaluated in cultured human lymphocytes by using sister chromatid exchanges (SCEs), chromosome aberration (CA), and micronucleus (MN) tests and also cell proliferation kinetics such as mitotic index (MI), replication index (RI), and nuclear division index (NDI) were analyzed for cytotoxicity. Cell cultures were treated with four different concentrations of dirithromycin (37.75, 67.50, 125, and 250 µg/mL) for 24 and 48 h periods. Dirithromycin significantly induced SCE and MN frequency at all concentrations in both 24 and 48 h treated cells. In addition, CA level has been markedly increased in the cells treated with almost all concentrations of dirithromycin for 24 (except 37.75 µg/mL) and 48 h treatment periods as compared to control. However, MI, RI, and NDI values were not affected by the dirithromycin treatment (p > 0.05). The results of this study indicated that dirithromycin treatment caused genetic damage by increasing the level of cytogenetic endpoints, suggesting its genotoxic and mutagenic action on human lymphocytes in vitro.

Highlights

Dirithromycin is a macrolide glycopeptide antibiotic and is used for the treatment of the mild-to-moderate infections, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin, as well as skin structure infections
Comparison of control and treated cells revealed that dirithromycin significantly increased the frequencies of chromosome aberration (CA)
Macrolide antibiotics include natural members, prodrugs, and semisynthetic derivatives and are composed of 14–16 member-ringed compounds. They are characterized by similar chemical structures and mechanism of action and resistance, they vary in the different pharmacokinetic parameters and spectrum of activity [2, 3]

Summary

Introduction

Dirithromycin is a macrolide glycopeptide antibiotic and is used for the treatment of the mild-to-moderate infections, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin, as well as skin structure infections. It is a prodrug and is developed for oral administration [1, 2]. Dirithromycin is converted by nonenzymatic hydrolysis during absorption to microbiologically active metabolite 9(S)-erythromycylamine. Sixty to 90% of the administered dose is hydrolysed to erythromycylamine within 35 minutes after dosing and conversion to erythromycin in serum is virtually completed after 1.5 hours. The primary route of elimination of erythromycin is faecal/hepatic [3,4,5]

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