Advantageous effect of low-molecular-weight heparin administration on hepatic mitochondrial redox state.
The effect of low-molecular-weight heparin (LMWH) on hepatic mithocondrial metabolism was compared with that of unfractionated heparin (UH) after the intravenous administration of these two kinds of heparin to normal rabbits. The magnitude of decrease in blood triglyceride levels 5 min after administration of UH (200 U/kg) was significantly greater than after LMWH (200 U/kg). Free fatty acid levels in the blood were significantly higher after this dose of UH than after LMWH. Blood total ketone body levels (acetoacetate + 3-hydroxybutyrate) 15 min after injection of 50 U/kg of UH were significantly higher than those after a dose of 50 U/kg of LMWH, and levels after 200 U/kg of UH were significantly higher than those after 200 U/kg of LMWH at 15, 30, 45 and 60 min. Enhanced ketogenesis was not noted after LMWH at any of the doses, or after UH at 3 U/kg. Arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial oxidation-reduction state (NAD+/NADH), was maintained above 1.0 in all groups except in the U-200 group, while AKBR in that group was significantly decreased to 0.99 +/- 0.14 at 30 min, and further decreased to 0.80 +/- 0.08 at 60 min. These results indicate that LMWH has less effect on lipolysis than UH and does not enhance ketogenesis, resulting in less deterioration of mitochondrial redox state.
Sasaki
H
H
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Yamaguchi
T
T
Kumada
K
K
Higashiyama
H
H
Terasaki
M
M
Mashima
S
S
Mitsuyoshi
A
A
Nakagami
M
M
Morimoto
T
T
Shimahara
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005227:Fatty Acids / Q000097:blood; D006493:Heparin / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007657:Ketone Bodies / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005227:Fatty Acids; D006495:Heparin, Low-Molecular-Weight; D007657:Ketone Bodies; D014280:Triglycerides; D006493:Heparin