title: The beneficial effect of ATP-MgCl(2) on hepatic ischemia/reperfusion-induced mitochondrial dysfunction.
abstract: The present study was undertaken to determine whether ATP-MgCl(2) administration in rats could protect hepatic mitochondrial function and improve energy metabolism during hepatic ischemia and subsequent reperfusion. Global hepatic ischemia was produced for 60 min followed by reperfusion. The rats then received 0.5 ml of saline or ATP-MgCl(2) intravenously. In saline-treated ischemic rats, serum alanine-aminotransferase levels peaked at 5 h. The aminotransferase level was significantly reduced in the ATP-MgCl(2) treatment group. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. ATP-MgCl(2) treatment minimized the increase in this ratio. The ketone body ratio in blood, which reflects the mitochondrial free NAD(+)/NADH ratio, decreased after ischemia and at 1 h following reperfusion. This decrease was somewhat improved by ATP-MgCl(2) infusion. At 1 and 5 h after reperfusion, mitochondrial monoamine oxidase and glutamate dehydrogenase activities decreased. ATP-MgCl(2) infusion following ischemia restored the lost activities. Hepatic ATP levels in saline-treated rats were found to be 50% lower 5 h following reperfusion; however, treatment with ATP-MgCl(2) resulted in significantly higher ATP levels and energy charge. The accumulation of purine catabolites in ischemic tissues was reduced during reperfusion. ATP-MgCl(2) infusion resulted in accumulation of adenosine in reperfused liver. Mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was inhibited by ATP-MgCl(2) infusion. The present results lead us to conclude that the amelioration of liver function which occurs with ATP-MgCl(2) infusion following ischemia may be mediated through improvement in ischemia-induced mitochondrial energy metabolism.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Changan-gu, Kyonggi-do 440-746, Suwon, South Korea.
authors.forename: C
authors.initials: C
authors.lastname: Jeong
authors.forename: S M
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000627:therapeutic use*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects; D007657:Ketone Bodies / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D015636:Magnesium Chloride / Q000627:therapeutic use*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000227:Adenine Nucleotides; D007657:Ketone Bodies; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases