NDLI: Clozapine-Induced Cardiotoxicity: Role of Oxidative Stress, Tumour Necrosis Factor Alpha and NF-κβ

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Clozapine-Induced Cardiotoxicity: Role of Oxidative Stress, Tumour Necrosis Factor Alpha and NF-κβ

Content Provider	Springer Nature Link
Author	Abdel Wahab, Basel A. Metwally, Metwally E.
Copyright Year	2014
Abstract	Safety concerns have been raised about clozapine-induced cardiotoxicity particularly in young patients. The exact mechanism of clozapine cardiotoxicity has not yet been thoroughly studied. This study aimed to investigate the possible mechanisms of clozapine-induced cardiotoxicity in a rat model. Young male Wistar rats were treated with clozapine (10, 15 and 25 mg/kg/day, i.p.) for 21 days. Haemodynamic and echocardiographic studies were performed for assessment of cardiac functions. Heart sections were studied histopathologically and immunohistochemically. Serum and cardiac markers of cardiotoxicity, oxidative stress, inflammation and apoptosis were evaluated. Heart sections of clozapine-treated animals showed increased cardiac inflammation that correlated with the clozapine dose. Serum levels of CK-MB and LDH levels increased, as did cardiac levels of TNF-α, MDA, NO, myeloperoxidase, 8-OHdG, caspase-3 and NF-κB p65. In contrast, GSH levels and GSH-Px activity decreased. Furthermore, immunohistochemical examination of the heart sections showed positive immunostaining for both 3-nitrotyrosine and caspase-3 in all clozapine-treated groups. Clozapine, particularly in relatively high doses, has a clear cardiotoxic effect. This cardiotoxicity is accompanied by increased myocardial oxidative stress, inflammatory cytokines, DNA damage and apoptosis with attenuation in antioxidant defences, thus explaining the previously reported myocarditis and pericarditis during clozapine therapy in clinical studies.
Starting Page	355
Ending Page	365
Page Count	11
File Format	PDF
ISSN	15307905
Journal	Cardiovascular Toxicology
Volume Number	15
Issue Number	4
e-ISSN	15590259
Language	English
Publisher	Springer US
Publisher Date	2014-12-25
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Clozapine Cardiotoxicity Oxidative stress TNF-α DNA damage NF-κB p65 Caspase-3 Pharmacology/Toxicology Cardiology
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Toxicology Cardiology and Cardiovascular Medicine

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