title: Endotoxemia impairs heart mitochondrial function by decreasing electron transfer, ATP synthesis and ATP content without affecting membrane potential.
abstract: Acute endotoxemia (LPS, 10 mg/kg ip, Sprague Dawley rats, 45 days old, 180 g) decreased the O₂ consumption of rat heart (1 mm³ tissue cubes) by 33% (from 4.69 to 3.11 μmol O₂/min. g tissue). Mitochondrial O₂ consumption and complex I activity were also decreased by 27% and 29%, respectively. Impaired respiration was associated to decreased ATP synthesis (from 417 to 168 nmol/min. mg protein) and ATP content (from 5.40 to 4.18 nmol ATP/mg protein), without affecting mitochondrial membrane potential. This scenario is accompanied by an increased production of O₂·⁻ and H₂O₂ due to complex I inhibition. The increased NO production, as shown by 38% increased mtNOS biochemical activity and 31% increased mtNOS functional activity, is expected to fuel an increased ONOO⁻ generation that is considered relevant in terms of the biochemical mechanism. Heart mitochondrial bioenergetic dysfunction with decreased O₂ uptake, ATP production and contents may indicate that preservation of mitochondrial function will prevent heart failure in endotoxemia.
authors.affiliation: Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Vanasco
authors.forename: Natalia D
authors.initials: ND
authors.lastname: Magnani
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Cimolai
authors.forename: Laura B
authors.initials: LB
authors.lastname: Valdez
authors.forename: Pablo
authors.initials: P
authors.lastname: Evelson
authors.forename: Alberto
authors.initials: A
authors.lastname: Boveris
authors.forename: Silvia
authors.initials: S
authors.lastname: Alvarez
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism*; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I