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[The effect of pentoxifylline on endotoxin-induced biopterin formation in rabbits]
1Trauma Center, 304th Hospital, People's Liberation Army, Beijing 100037, China.
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.