Evaluation of Azithromycin Induced Cardiotoxicity in Male Albino Rats and the Possible Protective Role of Nigella Sativa Oil

Abstract

Background: Azithromycin (AZ) is a broad spectrum macrolide antibiotic frequently used in treatment of bacterial infections. There are many cardiac adverse effects asso¬ciated with AZ treatment according to case reports and cohort studies. However, there are only few published experimental studies reported its cardiotoxicity in rats. Aim of the Work:The present work aimed to study the histopathological changes in the heart of male albino rat induced by AZ treatment. Also, to clarify the underlying mechanisms regarding oxidative stress, inflammatory marker release, apoptotic cell-death and myocardial fibrosis. Finally, the supposed protective effects of nigella sativa oil (NSO) co-treatment were assessed. Material and Methods: Twenty four adult male albino rats were divided into equal 4 groups; Control, AZ (30 mg/ kg/ day), AZ (30 mg/ kg/ day) +NSO (4 ml/ kg/ day), and NSO (4 ml/ kg/ day). The drugs were administrated intragastrically once daily for 2 weeks. Rats were sacrificed, blood and tissue samples were collected and processed for biochemical, histolopathological and immunohistochemical studies. Results: AZ treated group showed marked elevation in creatine phosphokinase (CPK), lactate dehydrogenase (LDH), Malondialdehyde (MDA), and tumor necrosis factor alpha (TNFα) levels. It induced significant myocardial necrosis, fibrosis, and apoptosis. It was the first time to demonstrate the effect of AZ on myofibroblasts proliferation by evaluating alpha smooth muscle actin (α-SMA) immunohitochemical expression which revealed significant increase after AZ treatment. Co-treatment with NSO significantly lowered CPK, LDH, MDA, and TNFα levels, preserved the cardiac morphology, and decreased Caspase-3 and αSMA immunoreactivity as compared to AZ group. Conclusion: Concluded that AZ induced cardiac adverse side effect in rats. NSO could prevent AZ-induced cardiotoxicity, and its mechanism may be related to antioxidant, antiinflammatory, antiapoptotic and antifibrotic properties. Further studies are required to confirm the efficacy of NSO as a protective agent in human AZ intoxication.

Nigella sativa L. Phytochemistry and Pharmacological Activities: A Review (2019–2021)

“…In another study, Azithromycin was able to induce myocardial necrosis, fibrosis, and apoptosis as well as increased creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), TNFα, and malondialdehyde and smooth muscle α-actin. Cotreatment with NSO significantly reduced CPK, LDH, MDA, and TNFα levels, preserved cardiac morphology, and decreased Caspase-3 and α-SMA immunoreactivity compared with the Azithromycin group [ 87 ]. Pei et al demonstrated the cardioprotective effect of TQ which was shown to be responsible for the decrease of lipid deposition at the cardiac tissue [ 92 ].…”