POSSIBLE CARDIAC ADVERSE EFFECTS OF THERAPEUTIC DOSES OF MACROLIDE ANTIBIOTICS (AZITHROMYCIN AND CLARITHROMYCIN) IN HEALTHY JUVENILE RATS: BIOCHEMICAL ASSESSMENT

Abstract

The macrolides antibiotics inhibit bacterial protein synthesis by an effect on translocation. They include erythromycin, azithromycin, clarithromycin, and roxithromycin . Their antimicrobial spectrum is varied. The drugs are associated with QT interval prolongation and cardiac dysrhythmias. This study was designed to determine whether or not a therapeutic oral dose of either azithromycin or clarithromycin administered for 5 or 10 days, respectively have cardiac adverse effects in healthy juvenile rats by assessing serum enzymes (CK-MB, LDH, AST and ALT), as markers of cardiac function. Twenty-eight healthy juvenile rats of both sexes weighing approximately 30gm were utilized and were randomly subdivided into 4 groups, control group orally-administered distilled water (DW) every 12hrs for 5 days via gavage tube, azithromycin suspension 12 mg/ kg every 12 hrs for 5 days via gavage tube, control group orally- administered DW every 12 hrs for 10 days via gavage tube and clarithromycin suspension 7.5 mg per kg for every 12 hrs for10 days via gavage tube. After scarification of animals by cervical dislocation, blood samples were taken by intra-cardiac puncture and utilized immediately to get serum in order to assess enzymes activities {heart creatin kinase isoform (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)}.The results of the present study demonstrated that were significant increase in serum activities of both CK-MB and LDH in group of animals treated with therapeutic oral dose of (12mg/kg) azithromycin for 5 days compared to the corresponding serum enzyme activities of control animals. While, there were no significant increase in serum activities of both AST and ALT in group of animals treated with therapeutic oral dose of (12mg/kg) azithromycin for 5 days compared to the corresponding serum enzyme activities of control group. Moreover, in groups of animals treated with therapeutic oral dose of (7.5mg/kg) clarithromycin for 10 days concerning the effect of the intended drug on serum activities of both CK-MB and LDH, there was significant increase in serum activities of both CK-MB and LDH in clarithromycin-treated rats compared to the corresponding serum enzyme activities of control animals. But, there were no significant increase in serum activities of both AST and ALT in rats treated with therapeutic oral dose of (7.5mg/kg) clarithromycin for 10 days compared to the corresponding serum enzyme activities of control animals. The results of this study provide an evidence, for the first time, to our knowledge on the effect of treatment of healthy juvenile rats with either azithromycin or clarithromycin , where both drugs have adverse effects on cardiac tissue manifested by increase in the levels of cardiac markers, (serum enzyme activities) especially CK-MB and LDH.; while, there were no change in serum activities of both AST and ALT compared to control rats. Thus, further studies are needed to confirm such finding.