Recovery of brain dopamine metabolism by branched-chain amino acids in rats with acute hepatic failure.
A decrease in the serum ratio of branched-chain amino acids (BCAAs) to aromatic amino acids (Fischer ratio) reflects the severity of hepatic encephalopathy, and clinical improvement by dietary augmentation with BCAAs has been demonstrated. As behavioral alteration results from changes in central neurotransmission, we investigated the role of BCAA administration on changes in the levels of central neurotransmitters in acute liver injury. Male Wistar rats were subjected to liver ischemia by occluding the left portal vein and hepatic artery for 90 minutes. A 4% BCAA solution containing valine, leucine, and isoleucine was intraperitoneally administered 3 times (8 mL/kg, each) at 1 hour, 6 hours, and 24 hours after vascular reperfusion, and changes in the extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were evaluated in the striatum by a microdialysis procedure. Although the extracellular concentration of dopamine was affected by neither liver ischemia nor BCAA injections, the level of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 34% in the ischemic group 24 hours after reperfusion. The 3,4-dihydroxyphenylacetic acid level was normalized by treatments with BCAAs. The improvement of deranged cerebral dopaminergic activity may be a contributing factor in the improvement of hepatic encephalopathy by BCAAs.
Deshpande
Gautam
G
Department of Internal Medicine, University of California-San Diego, San Diego, CA, USA.
Adachi
Naoto
N
Liu
Keyue
K
Motoki
Atsuko
A
Mitsuyo
Toshihiko
T
Nagaro
Takumi
T
Arai
Tatsuru
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood; D000596:Amino Acids / Q000097:blood; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000641:Ammonia / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000097:blood / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007511:Ischemia / Q000473:pathology; D008102:Liver Circulation / Q000502:physiology; D017114:Liver Failure, Acute / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood / Q000378:metabolism
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000641:Ammonia; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; D004298:Dopamine