title: A short-term high-dose administration of sodium pivalate impairs pyruvate metabolism without affecting cardiac function.
abstract: The pivalate moiety of some oral antibiotics enhances their intestinal absorption, but liberated pivalic acid decreases tissue carnitine concentration and could lead to impaired energy metabolism. The present study investigated the effects of short-term sodium pivalate administration on cardiac functionality and mitochondrial energy metabolism. Wistar rats received sodium pivalate (40 mM) in their drinking water for 14 days, and the carnitine content was measured in heart tissues. The activities of carnitine-dependent enzymes, including carnitine acetyltransferase (CrAT) and carnitine palmitoyltransferase I (CPT I), and the mitochondrial respiration rate were also measured. The isolated rat heart ischemia-reperfusion injury assay was performed based on the Langendorff technique through the reversible occlusion of the left anterior descending coronary artery. The administration of sodium pivalate decreased carnitine concentration in the myocardium by 37 %. Sodium pivalate significantly decreased mitochondrial respiration on pyruvate/malate by 28 %. The activities of CrAT and CPT I in sodium pivalate-treated animals were decreased by 34 and 30 %, respectively. No differences were observed in the infarct size or in the heart functional parameters between the groups. Together, these results indicate that the short-term administration of a high dose of sodium pivalate impairs cardiac mitochondrial energy metabolism without depressing cardiac function during ischemia-reperfusion injury.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia. janis_kuka@biomed.lu.lv
authors.forename: Janis
authors.initials: J
authors.lastname: Kuka
authors.forename: Marina
authors.initials: M
authors.lastname: Makrecka
authors.forename: Solveiga
authors.initials: S
authors.lastname: Grinberga
authors.forename: Osvalds
authors.initials: O
authors.lastname: Pugovics
authors.forename: Edgars
authors.initials: E
authors.lastname: Liepinsh
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D010421:Pentanoic Acids / Q000008:administration & dosage*; D019289:Pyruvic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D010421:Pentanoic Acids; C005566:pivalic acid; D019289:Pyruvic Acid