[The effect of pentoxifylline on endotoxin-induced biopterin formation in rabbits].
OBJECTIVE
To observe the potential effect of pentoxifylline on endotoxin-mediated biopterin (tetrahydrobiopterin and more oxidized species) formation and systemic hemodynamics.


METHODS
Rabbits were subjected to endotoxic shock induced by a bolus intravenous injection of E. coli O26B6 lipopolysaccharide (400 microg/kg). 28 animals were divided into sham-operation group (n = 8), endotoxic shock group (n = 10), and pentoxifylline-treated group (n = 10). Plasma biopterin and tumor necrosis factor-alpha (TNF) levels, and guanosine triphosphate cyclohydrolase I (GTP-CHI) activity in tissues were determined at various intervals.


RESULTS
Treatment with pentoxifylline significantly decreased plasma biopterin and TNF levels at 2 to 8 hours after endotoxin challenge (P < 0.05, P < 0.01), and inhibited GTP-CHI activities in the liver, lung, and myocardial tissues (P < 0.05). Meanwhile, systemic hemodynamic parameters, including mean arterial pressure, cardiac output, and total peripheral resistance, in the treatment group were much higher than those in the endotoxic shock group.


CONCLUSIONS
These data suggest that early treatment with pentoxifylline can effectively inhibit endotoxin-induced biopterin synthesis and release, and markedly improve systemic hemodynamics during septic shock.
Yao
Y
Y
Trauma Center, 304th Hospital, People's Liberation Army, Beijing 100037, China.
Yu
Y
Y
Peng
Z
Z
Dong
N
N
Chang
G
G
Sheng
Z
Z
D000818:Animals; D001708:Biopterins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006136:GTP Cyclohydrolase / Q000378:metabolism; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D011817:Rabbits; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D006136:GTP Cyclohydrolase; D010431:Pentoxifylline