title: Bone marrow mononuclear cells enhance anti-inflammatory effects of pravastatin against isoproterenol-induced myocardial infarction in rats.
abstract: The current study investigated the combinatorial effect of pravastatin (PRAV) and bone marrow mononuclear cells (BM-MNC) on acute myocardial infarction (AMI) induced experimentally in rats. After induction of MI, rats were given oral PRAV (20 mg/kg/day) for 28 days or a bolus intravenous injection (via lateral vein) of a total of 14 × 10(6) autologous BM-MNC or a combination of both. Serum brain natriuretic peptide (BNP) and histologic changes in cardiac tissues were assessed. Cardiac contents of lipid peroxides, superoxide dismutase (SOD) and inflammatory biomarkers including tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) were also measured. Combined PRAV and BM-MNC treatment significantly suppressed serum BNP. Cardiac cell apoptosis and inflammatory cell infiltration in heart tissue decreased significantly in both the PRAV and the PRAV + BM-MNC groups. Cardiac lipid peroxides along with TNFα and IL-1β levels were significantly reduced in both the PRAV and PRAV + BM-MNC hosts with an increase in SOD levels. However, the combined treatment increased cardiac NO levels and did not modify cardiac VEGF levels. The current results indicated that administration of BM-MNC improved the therapeutic efficacy of PRAV treatment by improving the morphology of infarcted hearts as well as decreasing inflammation in a host, but did not do so by inducing therapeutic angiogenesis.
authors.affiliation: a Pharmacology and Toxicology Department, Faculty of Pharmacy , Tanta University , Tanta , Egypt ;
authors.forename: Nageh
authors.initials: N
authors.lastname: El-Mahdy
authors.affiliation: b Zoology Department, Faculty of Science, Immunology and Biotechnology Unit, Immunology and Biotechnology Division , Center of Excellence in Cancer Research, Tanta University , Tanta , Egypt ;
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Salem
authors.affiliation: a Pharmacology and Toxicology Department, Faculty of Pharmacy , Tanta University , Tanta , Egypt ;
authors.forename: Magda
authors.initials: M
authors.lastname: El-Sayad
authors.affiliation: c Pathology Department, Faculty of Medicine , Tanta University , Tanta , Egypt.
authors.forename: Karima I
authors.initials: KI
authors.lastname: El-Desouky
authors.affiliation: a Pharmacology and Toxicology Department, Faculty of Pharmacy , Tanta University , Tanta , Egypt ;
authors.forename: Nesma
authors.initials: N
authors.lastname: Zaghow
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000276:immunology; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000009:adverse effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009000:Monocytes / Q000276:immunology* / Q000637:transplantation; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D009206:Myocardium / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D017035:Pravastatin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D020097:Natriuretic Peptide, Brain; D017035:Pravastatin; D007545:Isoproterenol
keywords: Pravastatin; anti-inflammatory effects; bone marrow mononuclear cells; isoproterenol; myocardial infarction