TY - JOUR
T1 - A short-term high-dose administration of sodium pivalate impairs pyruvate metabolism without affecting cardiac function
AU - Kuka, Janis
AU - Makrecka, Marina
AU - Grinberga, Solveiga
AU - Pugovics, Osvalds
AU - Liepinsh, Edgars
AU - Dambrova, Maija
N1 - Funding Information:
Acknowledgments The European Regional Development Fund grant No. 2010/0234/2DP/2.1.1.1.0/10/APIA/VIAA/063.
PY - 2012/12
Y1 - 2012/12
N2 - 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 carnitinedependent 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.
AB - 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 carnitinedependent 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.
KW - Carnitine
KW - Energy metabolism
KW - Heart mitochondria
KW - Ischemia-reperfusion injury
KW - Pivalate
UR - http://www.scopus.com/inward/record.url?scp=84870538032&partnerID=8YFLogxK
UR - https://www-proquest-com.db.rsu.lv/docview/1170539757/fulltextPDF/24AEE3C0B0434C7APQ/1?accountid=32994
U2 - 10.1007/s12012-012-9169-8
DO - 10.1007/s12012-012-9169-8
M3 - Article
C2 - 22539084
AN - SCOPUS:84870538032
SN - 1530-7905
VL - 12
SP - 298
EP - 303
JO - Cardiovascular Toxicology
JF - Cardiovascular Toxicology
IS - 4
ER -