Evaluation of Possible Genotoxic Activity of Dirithromycin in Cultured Human Lymphocytes

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.

Review: Eksplorasi Pemanfaatan Jamur Endofit pada Tanaman Curcuma dan Zingiber sebagai Penghasil Senyawa Antibakteri

“…Diritromisin yang dihasilkan oleh T. harzianum merupakan salah satu antibiotik golongan makrolida yang memiliki spektrum luas dalam menghambat pertumbuhan bakteri Gram-positif. Diritromisin tersebut memiliki mekanisme antibakteri dengan dihidrolisis secara nonenzimatik menjadi 9-(S)-erithromycilamine, erythromycylamine akan menempel pada subunit 50S pada 70S ribosom bakteri yang menyebabkan penghambatan sintesis protein pada bakteri target (Kayraldiz et al, 2015). Selain itu, Wang et al (2012) menemukan bahwa Chaetomium globosum yang merupakan jamur endofit yang terdapat pada Curcuma wenyujin mampu menghasilkan senyawa metabolit sekunder berupa chaetoglobosin X. Chaetoglobosin merupakan suatu senyawa metabolit sekunder dari jamur yang digolongkan sebagai alkaloid, yang mengandung gugus 10-(indol-3-yl) dengan cincin makrosilik.…”