Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse.
Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granulocytes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. Survival curves for CFU-S and GM-CFC showed that altered haematopoietic recovery in the INDO- and ESCUL-pretreated mice was not due to changes of intrinsic radiosensitivity of pluripotent (CFU-S) or committed (GM-CFC) stem cell populations. These results confirm earlier findings suggesting an inhibitory role of prostaglandins on haematopoiesis, and provide evidence that endogenous leukotrienes might play a positive role in the regulation of haematopoietic functions in an irradiated organism.
Kozubík
A
A
Institute of Biophysics, Academy of Sciences, Brno, Czech Republic.
Hofmanová
J
J
Pospísil
M
M
Netíková
J
J
Holá
J
J
Lojek
A
A
D000818:Animals; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011453:Prostaglandins / Q000502:physiology*; D014468:Umbelliferones / Q000494:pharmacology
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011453:Prostaglandins; D014468:Umbelliferones; C007628:esculetin; D007213:Indomethacin