Publications of Faculty of Medicine:The Beneficial Effect of Erdosteine Against Choloroquine-Induced Cardiotoxicity in Adult Male Albino Rats: A Biochemical and Histopathological Short-Term Study: Abstract

ABSTRACT Chloroquine (CQ) is a widely used drug to treat malaria as well as other autoimmune diseases such as rheumatoid arthritis and systemic lupus eiythematosus for several decades. Its toxic effects include retinopathy, myopathy, and neuropathy. In addition, serious cardiac complications may occur during long-term CQ therapy. Erdosteine (ES), a mucolytic drug used in chronic pulmonary diseases, is rich in sulphydryl thiol group, which accounts for free radical scavenging and antioxidant activity of the drug and plays a pivotal role in protecting cells against oxidative damage. Hence, the present study was undertaken to determine the protective role of ES against CQ-induced cardiotoxicity in rats through evaluation of some serum cardiac enzymatic parameters, various oxidants and antioxidants enzymatic activity levels in cardiac tissues, as well as histopathological changes of the myocardium. Forty adult male albino rats were divided into 4 equal groups (10 rats each) and each fasted group received its corresponding substance at a single dose per day orally after being dissolved in 1-ml of distilled water for 30 consecutive days as following: Group I (Control group; Cgp): Each rat had received 1-ml of distilled water; Group 2 (Erdosteine treated group; ES-gp): Each rat had received ES at 50 mg/kg; Group 3 (chloroquine treated group; CQ-gp): Each rat had received CQ at 15 mg/kg and Group 4 (erdosteine + chloroquine treated group; ES-CQ-gp): Each rat had received ED at 50 mg/kg two hours prior to administration of 15 mg/kg CQ. The obtained data from ES-gp, as compared to C-gp, showed non significant changes in rats' final body weights, absolute and relative heart weights, and cardiac troponin T (cTnT) levels, however, a significant decreases in serum total lactate dehydrogenase (LDH), total creatine phosphokinase (CPK), malondialdehyde (MDA), and myeloperoxidase (MPO) levels that accompanied with significant increases in reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) values were noticed. On the contrary, the results achieved from CQ-gp demonstrated several toxicological consequences in experimental animals. These findings were significant when compared with control parameters and included reduction in final body weights, gain in absolute and relative heart weights, biochemical elevations of serum LDH, CPK, and cTnT levels. Additionally, significant disturbance between oxidants/antioxidants balance measured in cardiac tissues were observed as increased MDA and MPO levels, accompanied with decreased GSH, SOD, and CAT values. Moreover, marked histopathological changes of myocardium in the form of waviness and disarrangement of the muscle fibers, variable degrees of cardiomyocytes degeneration, cellular enlargement with cytoplasmic vacuolization, and intense interstitial inflammatory cells infiltration were noticed. On the other side, administration of ES before CQ showed improvement of these alterations in biochemical indices and histopathologic changes that induced by CQ alone. This protective effects of ER against CQ associated different metamorphoses is possibly achieved by preventing free radical damaging cascades, oxidant radical release, and proinflammatory processes. In conclusion,the results of this experimental study suggest that ES has cardioprotective effects against CQ induced cardiac injury in adult male albino rats. Thus, patients on long term CQ administration making them prone to cardiac injury and hence co-administration of erdosteine may have beneficial effects in reducing the occurrence of this incidence.