Effect of platelet-activating factor antagonist and leukotriene antagonist on endotoxin shock in the rat: role of the leukocyte.
The effects of platelet-activating factor (PAF) antagonist (CV-3988) and leukotrienes (LTs) antagonist (ONO-1078) on endotoxin-induced sequelae in the rat were assessed. Pretreatment with either CV-3988 (6 mg/kg, i.v.) or ONO-1078 (150 mg/kg, p.o.) did not improve survival rate following the administration of Escherichia coli lipopolysaccharide (LPS) compared with that of control rats pretreated with solvents of the drugs. Rats pretreated with both CV-3988 and ONO-1078 exhibited significantly (P less than 0.01) enhanced survival following lipopolysaccharide (LPS) administration. Percentage survivals 48 hr after the administration of LPS were 20%, 32%, 24%, and 68% in the pretreatment with solvents, CV-3988, ONO-1078, and CV-3988 combined with ONO-1078 groups, respectively. Pretreatment with CV-3988 combined with ONO-1078 inhibited the change of plasma transaminase 3 hr after LPS administration. The neutropenia, due to the administration of vinblastine (1 mg/kg, i.v.), increased the survival rate following the administration of LPS without pretreatment with PAF and LT antagonists. Antishock action of CV-3988 and ONO-1078 could not be seen in neutropenic rats. These data suggest that combined pretreatment with PAF antagonist and LT antagonist inhibited leukocyte-mediated tissue injury in LPS-induced endotoxemia.
Yoshikawa
D
D
Department of Anesthesiology and Resuscitology, Gunma University School of Medicine, Japan.
Goto
F
F
D000818:Animals; D002867:Chromones / Q000627:therapeutic use*; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D020024:Leukotriene Antagonists; D008297:Male; D009503:Neutropenia / Q000503:physiopathology; D010742:Phospholipid Ethers / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D014747:Vinblastine / Q000627:therapeutic use
D002867:Chromones; D020024:Leukotriene Antagonists; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D014747:Vinblastine; C037913:CV 3988; C047681:pranlukast