Stimulated recovery of perturbed haematopoiesis by inhibition of prostaglandin production — promising therapeutic strategy

Höfer, Milan; Pospı́šil, M.

doi:10.2478/s11535-006-0033-3

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…A number of studies were performed testing the effects of non-selective COX inhibitors on hematopoiesis suppressed by ionizing radiation. The results of these studies are presented in more detail in earlier reviews [2,55]. Briefly, non-selective COX inhibitors, like indomethacin, diclofenac, and flurbiprofen, were reported to enhance mouse hematopoiesis when administered singly before or after one-time-sublethal irradiation, in the course of fractionated irradiation [56,57,58], as well as when given concomitantly with immunomodulators [59,60,61] or chemical radioprotectors [62].…”

Section: Effects Of Non-selective Cox Inhibitors In Sublethally Anmentioning

confidence: 99%

Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome

2019

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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.

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Section: Effects Of Non-selective Cox Inhibitors In Sublethally Anmentioning

confidence: 99%

Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome

2019

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“…Various non-selective cyclooxygenase inhibitors were reported to stimulate proliferation of hematopoietic stem cells [27], to enhance bone marrow and splenic hematopoiesis [28,29], and bone marrow erythropoiesis [30] in mice. Many studies have been performed by several research groups on the topic of experimental treatment of hematopoiesis suppressed by ionizing radiation (described in more detail in an earlier review [31]). Positive therapeutical outcomes, manifested as an enhancement of murine hematopoiesis after radiation damage, were reported when NSAIDs (indomethacin, diclofenac, or flurbiprofen) were administered before [32,33,34,35] or after irradiation [36,37,38], as well as when given to mice exposed to fractionated irradiation [39,40,41], to continuously irradiated rats [42], or lethally irradiated mice who received syngeneic bone marrow transplantation [43,44].…”

Section: Action Of Non-selective Cyclooxygenase Inhibitors On Hemamentioning

confidence: 99%

Stimulatory Action of Cyclooxygenase Inhibitors on Hematopoiesis: A Review

et al. 2012

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Abstract:The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E 2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts the feedback to positive control. Based on these relationships, agents inhibiting cyclo-oxygenases, known as non-steroidal anti-inflammatory drugs (NSAIDs), can activate hematopoiesis and be protective or curative under myelosuppressive states. The effectiveness of therapeutic use of NSAIDs in these situations is expressive especially under the selective inhibition of cyclooxygenase-2 (COX-2), when undesirable side effects of cyclooxygenase-1 inhibition, like gastrointestinal damage, are absent. The effects of the clinically approved selective COX-2 inhibitor, meloxicam, were investigated and demonstrated significant hematopoiesis-stimulating and survival-enhancing actions of this drug in sublethally or lethally γ-irradiated mice. These effects were connected with the ability of meloxicam to increase serum levels of the granulocyte colony-stimulating factor. It can be inferred from these findings that selective COX-2 inhibitors might find their use in the treatment of myelosuppressions of various etiologies.

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“…Prostaglandin E 2 was found to participate in the regulation of hematopoiesis and to play an important role in the negative hematopoietic feedback control [11,12]. Previous studies from our laboratory have shown that non-selective NSAIDs, like indomethacin, diclofenac, ibuprofen, or flurbiprofen, stimulate hematopoiesis in sublethally irradiated mice when administered before or after irradiation (reviewed in [13]). However, when non-selective NSAIDs were administered to lethally irradiated mice, their survival was observed to be significantly lower in comparison with control animals; this observation could be ascribed to the lack of COX-1 in the gastrointestinal tract where prostaglandins play a protective role [13].…”

Section: Introduction To Radiobiological Studies On Cyclooxygenase Inmentioning

confidence: 99%

“…Previous studies from our laboratory have shown that non-selective NSAIDs, like indomethacin, diclofenac, ibuprofen, or flurbiprofen, stimulate hematopoiesis in sublethally irradiated mice when administered before or after irradiation (reviewed in [13]). However, when non-selective NSAIDs were administered to lethally irradiated mice, their survival was observed to be significantly lower in comparison with control animals; this observation could be ascribed to the lack of COX-1 in the gastrointestinal tract where prostaglandins play a protective role [13]. An increased intestinal damage caused by the combination of lethal irradiation and administration of non-selective NSAIDs was also experimentally proved [14].…”

Section: Introduction To Radiobiological Studies On Cyclooxygenase Inmentioning

confidence: 99%

Combined pharmacological therapy of the acute radiation disease using a cyclooxygenase-2 inhibitor and an adenosine A3 receptor agonist

et al. 2014

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Combined approaches to the treatment of acute radiation disease are preferred to single-agent therapies due to proven or anticipated better outcomes comprising increased therapeutic efficacy and decreased incidence of undesirable side effects. Our studies on post-exposure treatment of mice irradiated by sublethal or lethal doses of ionizing radiation included testing the effectiveness of meloxicam, a cyclooxygenase-2 inhibitor, and IB-MECA, an adenosine A3 receptor agonist. The efficacy of meloxicam and IB-MECA to positively influence the progress of the acute radiation disease has been tested in situations of their combined administration with granulocyte colony-stimulating factor (G-CSF) or with each other. The results of our studies revealed a significantly improved regeneration of hematopoietic cell populations ranging from the bone marrow progenitor cells to mature blood cells following combined treatments. Also, survival of mice exposed to lethal radiation doses was highest in the animals treated with a combination of the two drugs. It can be inferred from the results that if the drug combinations employed were used in humans, e.g. in the treatment of victims of radiation accidents, a better therapeutic outcome could be expected. Therefore, further studies directed at clinical applications of meloxicam and IB-MECA in radiation victims is recommended.

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Stimulated recovery of perturbed haematopoiesis by inhibition of prostaglandin production — promising therapeutic strategy

Cited by 8 publications

References 36 publications

Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome

Brief Story on Prostaglandins, Inhibitors of their Synthesis, Hematopoiesis, and Acute Radiation Syndrome

Stimulatory Action of Cyclooxygenase Inhibitors on Hematopoiesis: A Review

Combined pharmacological therapy of the acute radiation disease using a cyclooxygenase-2 inhibitor and an adenosine A3 receptor agonist

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