Exploring the protective role of apocynin, a specific NADPH oxidase inhibitor, in cisplatin-induced cardiotoxicity in rats.

Abstract

Despite the clinical reports, few studies have focused on reducing the cardiotoxicity of cisplatin. In the present study, cardiotoxicity was examined after a single ip injection of cisplatin (7mg/kg) in rats. Apocynin was given in drinking water (600mg/L) for five successive days before and after cisplatin injection. At the end of the experiment, hemodynamic parameters were recorded, animals were sacrificed and serum creatine kinase-MB activity was determined. The whole ventricle was isolated for estimation of tumor necrosis factor-alpha (TNF-α) content, NADPH oxidase, myeloperoxidase and caspase-3 activities in addition to nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nuclear factor kappa B (NF-κB) gene expressions. Furthermore, oxidative stress markers and antioxidant enzymes were measured in postmitochondrial and mitochondrial fractions. Mitochondrial membrane potential, nuclear DNA fragmentation and cardiomyocyte cross-sectional area were also evaluated. Apocynin was effective against cisplatin-induced decrement in heart rate and blood pressure. Moreover, pretreatment with apocynin notably ameliorated the state of oxidative stress, mitigated inflammation and preserved mitochondrial membrane potential. Apocynin provided also a significant cardioprotection as revealed by alleviating the overexpression of Nrf2, HO-1 and NF-κB, the elevation of caspase-3 activity, the prominent nuclear DNA fragmentation and the decreased cardiomyocyte cross-sectional area. This study highlights the potential role of apocynin in inhibiting cisplatin-induced hemodynamic changes, postmitochondrial and mitochondrial damage as indicated by improvement in the state of oxidative stress, inflammation and apoptosis.

• Authors: Maha M El-Sawalhi, Lamiaa A Ahmed
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 207 Pg. 58-66 (Jan 25 2014) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 24291008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Acetophenones
• Biomarkers
• Cardiotonic Agents
• Enzyme Inhibitors
• acetovanillone
• NADPH Oxidases
• Creatine Kinase
• Cisplatin

Topics

• Acetophenones (pharmacology, therapeutic use)
• Animals
• Biomarkers (metabolism)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Cardiovascular Diseases (blood, chemically induced, drug therapy, enzymology)
• Cisplatin (adverse effects)
• Creatine Kinase (blood)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Gene Expression Regulation (drug effects)
• Heart Rate (drug effects)
• Male
• Mitochondria, Heart (drug effects, metabolism)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar