Metabolic disposition of leukotriene B₄ (LTB4) and oxidation‐resistant analogues of LTB4 in conscious rabbits

Abstract

1 The kinetics of leukotriene B4 (LTB4), after single i.v. injections of doses of 0.1 to 1 fig kg-', were investigated in conscious rabbits and compared with those of the Q-and 13-oxidation resistant bioactive analogues, 20, 20, 0.53 ± 0.03 min, and an apparent Vd of 85 ± 9 ml kg-, similar to the parameters obtained after LTB4 boluses.5 The disposition of LTB4 analogues, whether resistant to a-or to P-oxidation in vitro, did not differ significantly from the disposition of the LTB4 molecule. The half-lives of 20-F3-LTB4 and 3-thio-LTB4 in the circulation were 0.52 ± 0.07 min and 0.70 ± 0.11 min, respectively. 6 In summary, our results showed that LTB4, as well as a-oxidation-and P-oxidation-resistant analogues were cleared very rapidly from the rabbit circulation and indicate that in situ, metabolism in blood is not a rate-limiting factor for the elimination of LTB4.

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

“…One striking observation from these animal studies is that the peak pharmacodynamic effects triggered by LTB 4 long outlasted the presence of plasmatic LTB 4 . In fact, as observed previously (56), the elimination of LTB 4 from the circulation is very rapid, with Ͼ90% of the LTB 4 injected eliminated within 15 min. These results suggest that the biological effects triggered by LTB 4 are maintained for several hours.…”

Blocking Macrophage Leukotriene B 4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension

“…Serum levels of LTB 4 were significantly elevated in PAH patients, especially in those with connective tissue disease-associated PAH (CTD-PAH). The half-life of LTB 4 is only several minutes (66), and it is unknown how well serum LTB 4 approximates lung LTB 4 levels. In a smaller cohort of PAH patients, lung LTB 4 levels were not significantly increased, although a trend toward increased LTB 4 was seen in secondary PAH patients, a group that presumably included CTD-PAH patients (67).…”

Trauma and hemorrhagic shock activate molecular association of 5-lipoxygenase and 5-lipoxygenase–Activating protein in lung tissue

“…This assay measures aggregate levels of LTC 4 , LTD 4 , LTE 4 , all of which are produced from arachidonic acid breakdown from the ALOX/ALOX5AP pathway. We did not assay LTB4 due to the rapid metabolism in vivo (9).…”