Administration of tumor necrosis factor-alpha results in a decreased placental transfer of amino acids in the rat.
The administration of an acute tumor necrosis factor-alpha (TNF) dose (100 micrograms/kg BW) to 20-day pregnant rats resulted in a substantial decrease in the fetal availability of maternally administered amino acids, as measured by the accumulation of alpha-amino-[1-14C]isobutyrate ([14C]AIB) and [1-14C]cycloleucine ([14C]CLEU), nonmetabolizable analogs of the amino acids alanine and leucine, respectively. Thus, TNF treatment resulted in a decreased accumulation of the tracers in the whole fetus as well as in fetal liver. The cytokine also caused important changes on the maternal liver, where it increased both [14C]AIB and [14C]CLEU accumulation. In skeletal muscle and heart, TNF treatment resulted in decreased [14C]AIB accumulation, but increased [14C]CLEU. These changes in tissue amino acid uptake were accompanied by changes in circulating amino acids. TNF treatment promoted an increase in the concentrations of both alanine and leucine in the maternal circulation, whereas no changes in the circulating concentrations of these amino acids were observed in the fetuses. The decreased fetal accumulation of maternally derived amino acid analogs is partially explained by a decrease in fetal blood flow [as measured by the accumulation of [14C]1,1,1-trichloro-2,2- bis-(p-chlorophenyl)ethane] induced by the cytokine). It is suggested that the cytokine may be involved in fetal growth impairment during pathological states (such as tumor growth or chronic infection) by promoting a decreased transplacental passage of amino acids, essential compounds for both protein accretion and oxidation in fetal metabolism.
Carbó
N
N
Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Spain.
López-Soriano
F J
FJ
Argilés
J M
JM
D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003515:Cycloleucine / Q000493:pharmacokinetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D007328:Insulin / Q000097:blood; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D003515:Cycloleucine