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[Biopterin synthesis and GTP cyclohydrolase I mRNA expression in rats following endotoxic shock]
1Trauma Research Center, 304th Hospital, People's Liberation Army, Beijing 100037.
Objective:
To investigate the potential role of changes in biopterin (tetrahydrobiopterin and more oxidized species) synthesis and GTP cyclohydrolase I (GTP-CHI) mRNA expression in endotoxic shock.
Methods:
SD rats were subjected to endotoxic shock by a bolus injection of lipopolysaccharide (15 mg/kg, i.p.), biopterin and GTP-CHI mRNA levels in liver, kidney, and intestine were determined at 4, 8 hours following endotoxin challenge.
Results:
Tissue biopterin levels significantly elevated in liver, kidney, and intestine, with high levels sustaining for 8 hours after endotoxin challenge (P < 0.05, P < 0.01). Similarly, GTP-CHI mRNA induction in various tissues substantially increased within 4 hours compared to normal controls (P < 0.05, P < 0.01). It was also shown that hepatic and renal biopterin levels were positively correlated with glutamic pyruvic transaminase (GPT) and also blood urea nitrogen (BUN) values (both P < 0.01). In addition, treatment with recombinant bactericidal/permeability increasing protein (rBPI(21)) markedly reduced tissue biopterin and GTP-CHI mRNA levels, concomitant with significant decreases in GPT, BUN as well as D-lactate values.
Conclusions:
Biopterin synthesis and release may be involved in the development of endotoxin-induced multiple organ dysfunction, and early use of rBPI(21) is effective to inhibit marked GTP-CHI mRNA expression and biopterin formation following septic shock.
