Abstract
Prostaglandins and inhibitors of their synthesis (cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs) were shown to play a significant role in the regulation of hematopoiesis. Partly due to their hematopoiesis-modulating effects, both prostaglandins and COX inhibitors were reported to act positively in radiation-exposed mammalian organisms at various pre- and post-irradiation therapeutical settings. Experimental efforts were targeted at finding pharmacological procedures leading to optimization of therapeutical outcomes by minimizing undesirable side effects of the treatments. Progress in these efforts was obtained after discovery of selective inhibitors of inducible selective cyclooxygenase-2 (COX-2) inhibitors. Recent studies have been able to suggest the possibility to find combined therapeutical approaches utilizing joint administration of prostaglandins and inhibitors of their synthesis at optimized timing and dosing of the drugs which could be incorporated into the therapy of patients with acute radiation syndrome.
Highlights
Prostaglandins, as well as inhibitors of their synthesis, act in hematopoiesis through a spectrum of pleiotropic effects [1,2]
Much work on the topic of pharmacological modulation of radiation damage by prostaglandins was done by the group of Hanson et al They showed that various prostaglandin derivatives, like 16,16dimethyl Prostaglandin E2 (PGE2) [9], or misoprostol, a prostaglandin E1 analog [35], protected intestinal stem cells from deleterious effects of ionizing radiation
Meloxicam is the only selective COX-2 inhibitor investigated in more detail from the point of view of testing its hematopoiesis-stimulating abilities in the situation of the acute radiation syndrome inducing radiation exposure
Summary
Prostaglandins, as well as inhibitors of their synthesis, act in hematopoiesis through a spectrum of pleiotropic effects [1,2]. Subsequent studies, especially of radiobiological and hematological targeting, brought new pieces of information about the contribution of prostaglandins and inhibitors of their synthesis to the regulation of hematopoiesis under normal and perturbed conditions. Some of these studies uncovered new possibilities on how to enhance recovery following an exposure to sublethal or lethal radiation doses [9,10]. In vitro studies from 1982 have reported a stimulated production of cycling hematopoietic progenitor cells from a population of quiescent, non-cycling cells, most likely of stem cells from mouse or human bone marrow exposed to PGE2 [24]. Detailed analysis of methodological aspects of hematological studies on PGE2 and other eicosanoids, as well as of mechanisms of their effects, can be found in a separate review [1]
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