Prophylactic effects of tetramethyl pyrazine on mice with endotoxemia and its relationship with platelet-activating factor.

Abstract

Aim: To study the prophylactic effects of tetramethyl pyrazine (TMP) on mice with endotoxemia and its relationship with platelet-activating factor (PAF).

Methods: LD80 of lipopolysaccharides (LPS, 15 mg.kg-1) was injected into mice (i.v.) pretreated with TMP (i.p.). The survival rate and the level of serum PAF were observed. The PAF induced by LPS in vivo and in vitro, and the activities of PLA2 and acetyl-CoA: lyso-PAF acetyltransferase were determined.

Results: TMP (10, 30, 90 mg.kg-1) obviously lowered the mortality of mice and also dose-dependently decreased the level of serum PAF [(25.5 +/- 1.7), (13.4 +/- 3.2), (9.6 +/- 2.1) micrograms.L-1, vs control (29.3 +/- 2.1) micrograms.L-1, P < 0.01]. TMP (0.05, 0.5, 5, 50 mumol.L-1) dose-dependently decreased the release of PAF [(12.7 +/- 1.6), (8.9 +/- 1.2), (6.9 +/- 0.8), (5.5 +/- 1.0) micrograms.L-1 vs control (11.9 +/- 1.8) micrograms.L-1, P < 0.01] from PMO cultured with LPS (5 mg.L-1), reduced the PLA2 activity [(149.9 +/- 2.8), (117.5 +/- 2.0), (89.6 +/- 2.0), (75.0 +/- 2.8) U vs control (170.8 +/- 3.9) U, P < 0.01] and acetyl-CoA: lyso-PAF acetyltransferase activity [PAF (9.5 +/- 0.7), (5.2 +/- 0.7), (2.9 +/- 0.3), (2.5 +/- 0.3) micrograms.g-1 (protein).min-1 vs control (11.0 +/- 0.7) micrograms.g-1 (protein).min-1, P < 0.01] of PMO lysate.

Conclusion: TMP protected the mice with endotoxemia from the death by decreasing the biosynthesis of PAF through the inhibition of the activities of PLA2 and acetyl-CoA: lyso-PAF acetyl-transferase.