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Prophylactic effects of tetramethyl pyrazine on mice with endotoxemia and its relationship with platelet-activating
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.
Insights
Tetramethyl pyrazine (TMP) protects mice from endotoxemia by reducing platelet-activating factor (PAF) biosynthesis. This study shows TMP inhibits key enzymes involved in PAF production, lowering mortality rates in endotoxemic mice.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Endotoxemia is a life-threatening condition caused by bacterial endotoxins.
- Platelet-activating factor (PAF) plays a crucial role in the inflammatory response during endotoxemia.
- Tetramethyl pyrazine (TMP) is a compound with potential anti-inflammatory properties.
Purpose of the Study:
- To investigate the protective effects of tetramethyl pyrazine (TMP) against endotoxemia in a mouse model.
- To elucidate the relationship between TMP's prophylactic effects and platelet-activating factor (PAF) levels.
- To determine the impact of TMP on PAF biosynthesis pathways.
Main Methods:
- Mice were challenged with lipopolysaccharides (LPS) to induce endotoxemia.
- Pretreatment with varying doses of TMP was administered.
- Survival rates, serum PAF levels, and PAF-induced enzyme activities (PLA2, acetyl-CoA: lyso-PAF acetyltransferase) were measured in vivo and in vitro.
Main Results:
- TMP significantly reduced mortality in LPS-induced endotoxemic mice in a dose-dependent manner.
- Serum PAF levels were significantly decreased by TMP treatment.
- TMP inhibited LPS-induced PAF release from peritoneal macrophages (PMO) and reduced the activity of PLA2 and acetyl-CoA: lyso-PAF acetyltransferase.
Conclusions:
- Tetramethyl pyrazine (TMP) demonstrates prophylactic effects against endotoxemia in mice.
- TMP exerts its protective effects by inhibiting PAF biosynthesis.
- The mechanism involves the suppression of PLA2 and acetyl-CoA: lyso-PAF acetyltransferase activities, thereby reducing PAF production.