Mohamed M. Elkhawanky MD-PhD; Associate professor of Clinical Hematopathology in College of Medicine, Najran University, Saudi Arabia. He is a founding member of the PBL Medical Education Committee at the Najran University. Dr. Elkhawanky received his medical degree from College of Medicine, Zagazig University, Egypt in 1999. He subsequently completed a 3-years residency program at Zagazig University Hospitals. He holds MD-PhD in Clinical Hematopathology from College of Medicine, AL-Azhar University. Dr. Elkhawanky conducts several funded research projects concerning medical problems and their solutions and has published widely. He has been invited to speak at several international scientific conferences.


Clozapine is an atypical antipsychotic drug selectively effective in the treatment of refractory schizophrenia. However, myocarditis, as a serious cardiotoxic effect, has in several case reports been associated with clozapine therapy. An increase in the free radical production and ischemia, probably induced by clozapine-induced release of catecholamines, have been hypothesized to trigger an inflammatory response that leads to the clinically observed cardiomyopathy and sudden death even in young patients. The aim of this work is to study the role of oxidative stress in clozapine induced myocarditis and myocardial DNA damage in a rat model. Methods: Male Wistar rats, age _6 weeks, were administered 5, 10 or 25 mg/kg clozapine daily for 21 days; saline-treated rats served as the control. Heart sections were stained with hematoxylin and eosin for histopathological examination. Plasma CK-MB, LDH and TNF-α concentrations were determined. Myocardial oxidative stress (MDA and NO), antioxidant (GSH and GSH-Px) parameters, and the marker of oxidative DNA damage (8-OHdG) were determined. Results: Clozapine treatment resulted in significant dose-related increases in myocardial inflammation with increased plasma TNF-a, CK-MB and LDH levels. Myocardial MDA, NO and serum and cardiac 8-OHdG levels increased while GSH level and GSH-Px activity decreased with the highest significance seen with the largest tested dose (25 mg/kg) of clozapine. Conclusions: Clozapine, in relatively large doses induced myocarditis consistently with increased myocardial oxidative stress, DNA damage and inflammatory cytokines in a rat mode.