title: Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.
abstract: Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers.
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Lakshmikanthan
authors.initials: L
authors.lastname: Panneerselvam
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Vimal
authors.initials: V
authors.lastname: Govindarajan
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Jaishabanu
authors.initials: J
authors.lastname: Ameeramja
authors.affiliation: Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills P.O, Kottayam 686 560, Kerala, India.
authors.forename: Harikumaran Raveendran
authors.initials: HR
authors.lastname: Nair
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India. Electronic address: ekas2009@buc.edu.in.
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Perumal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002327:Cariostatic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000506:poisoning*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005458:Fluoride Poisoning / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D012969:Sodium Fluoride / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000506:poisoning*; D014018:Tissue Distribution; D066007:Toxicokinetics; D018754:Ventricular Dysfunction / Q000209:etiology
chemical_list: D015415:Biomarkers; D002327:Cariostatic Agents; D012969:Sodium Fluoride; D010088:Oxidoreductases; D005978:Glutathione
keywords: Apoptosis; Fluoride; Heart; Myofibrillar lysis; Necrosis; Serum