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The effects of a highly selective 5-lipoxygenase inhibitor, CGS8515 [methyl 2-[(3,4-dihydro-3,4-dioxo-1-naphthalenyl) amino]benzoate], on endotoxic shock sequelae and eicosanoid synthesis by peritoneal macrophages were evaluated in the rat. Pretreatment of peritoneal macrophages in vitro with CGS8515 significantly inhibited the synthesis (P less than .01) of immunoreactive leukotriene C4/leukotriene D4 stimulated by the calcium ionophore (A23187). Inhibition of 5-lipoxygenase produced significant shunting to immunoreactive thromboxane B2 formation (P less than .05). In rats sedated with ketamine.HCl (82.5 mg/kg) and xylazine. HCl (27.5 mg/kg), i.v. injection of Salmonella enteritidis endotoxin (25 mg/kg i.v.) produced significant decreases at 30 min in mean arterial pressure (from 89 +/- 4 to 44 +/- 8 mm Hg, N = 5, P less than .001); in white blood cell count (from 10.8 +/- 0.6 to 6.5 +/- 0.8 x 10(3)/mm3, N = 5, P less than .01); in platelet count (from 687 +/- 66 to 392 +/- 65 x 10(3)/mm3, N = 5, P less than .01); and produced an increase of hematocrit (from 46 +/- 1.2 to 57.4 +/- 1.8%, N = 5, P less than .03). CGS8515 (5 mg/kg i.v. 30 min before endotoxin injection, N = 6) blunted the endotoxin-induced hypotension by 35% (P less than .001), the leukopenia by 24% (P less than .03), the thrombocytopenia by 45% (P less than .006) and the hemoconcentration by 16% (P less than .03), compared to the shocked control rats 30 min after endotoxin injection.(ABSTRACT TRUNCATED AT 250 WORDS)
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
January 1983,
British journal of clinical pharmacology,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
March 1984,
Prostaglandins, leukotrienes, and medicine,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
June 1997,
Prostaglandins, leukotrienes, and essential fatty acids,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
May 2007,
Critical care medicine,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
July 1994,
Shock (Augusta, Ga.),
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
January 1997,
Life sciences,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
February 1990,
Arzneimittel-Forschung,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
April 1983,
British journal of pharmacology,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
October 2004,
The new microbiologica,
G Matera, and
J A Cook, and
R A Hennigar, and
G E Tempel, and
W C Wise, and
T D Oglesby, and
P V Halushka
March 1985,
Pharmacological research communications,
