title: 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.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Maha M
authors.initials: MM
authors.lastname: El-Sawalhi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: lamiaahmed@Staff.cu.edu.eg.
authors.forename: Lamiaa A
authors.initials: LA
authors.lastname: Ahmed
mesh_terms: D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology; D002945:Cisplatin / Q000009:adverse effects*; D003402:Creatine Kinase / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000098:Acetophenones; D015415:Biomarkers; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; C056165:acetovanillone; D019255:NADPH Oxidases; D003402:Creatine Kinase; D002945:Cisplatin
keywords: Apocynin; Cardiotoxicity; Cisplatin; Inflammation; Oxidative stress