On Radiation Damage to Normal Tissues and its Treatment: II. Anti-inflammatory drugs

Michałowski, A.

doi:10.3109/02841869409098397

Cited by 95 publications

(42 citation statements)

References 218 publications

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“…The mechanism by which irradiation leads to an increase in ROS is not known; however, it has been shown that exposure of thymocytes to irradiation leads to metabolism of arachidonic acid by lipoxygenase (41), and this action can lead to the generation of ROS. It has also been reported that irradiation increases generation of eicosanoids (42) including prostaglandin E 2 (42,43), which is produced by the action of cyclooxygenase on arachidonic acid. The role of eicosanoids in the inflammatory response is well documented (44), and therefore these findings are consistent with the idea that irradiation induces inflammation.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Lonergan¹,

Martin²,

Horrobin³

et al. 2002

Journal of Biological Chemistry

112

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Exposure to irradiation leads to detrimental changes in several cell types. In this study we assessed the changes induced in hippocampus by exposure of rats to whole body irradiation; the findings reveal that irradiation leads to apoptotic cell death in hippocampus, and as a consequence, long term potentiation in perforant path-granule cell synapses is markedly impaired. The evidence is consistent with the view that irradiation induced an increase in reactive oxygen species and that this leads to stimulation of the stress-activated protein kinase, JNK, and activation of the transcription factor, c-Jun. Consequent upon activation of JNK, a cascade of cell signaling events was stimulated that ultimately resulted in apoptosis, as suggested by parallel increases in cytochrome c translocation, caspase-3 activation, poly-(ADP-ribose) polymerase cleavage, and terminal dUTP nick-end labeling staining. Treatment of rats with eicosapentaenoic acid inhibited the irradiation-induced increase in reactive oxygen species production and the subsequent cellular signaling events, suggesting that oxidative stress triggered apoptotic cell death in the hippocampus of rats exposed to irradiation. Significantly, when the compromise in cell viability induced by irradiation was prevented by eicosapentaenoic acid, long term potentiation was sustained in a manner similar to that in the sham-treated control group.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Lonergan¹,

Martin²,

Horrobin³

et al. 2002

Journal of Biological Chemistry

112

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“…The above studies revealed that NSAIDs enhanced a wide range of haematological parameters in experimental animals, including those illustrating the state of the compartments of multipotent and committed progenitor cells, total cellularity of haematopoietic organs, and numbers of mature peripheral blood cells. In 1994 the positive results with NSAIDs on stimulation of haematopoiesis obtained in animal experiments directed A.S. Michalowski to state that "Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable" [46]. Nevertheless, administration of classical NSAIDs, including those tested in the above-mentioned studies, is frequently accompanied by undesirable side effects.…”

Section: Hematopoiesis and Non-selective Cyclooxygenase Inhibitorsmentioning

confidence: 99%

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

Höfer

Pospı́šil

2006

Open Life Sciences

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Abstract:Inhibitors of prostaglandin production, designated as classical non-steroidal antiinflammatory drugs (NSAIDs) and acting on the base of non-selective inhibition of cyclooxygenases, have been found in numerous studies to potentiate recovery of perturbed haematopoiesis by removing the negative feedback control mediated by prostaglandins. However, classical NSAIDs show pronounced undesirable gastrointestinal side effects, which limits the possibility of their utilization for various pathophysiological states including myelosuppression. Specific cyclooxygenase-2 (COX-2) inhibitors, targeted at selective inhibition of this inducible cyclooxygenase isoform and having much better gastrointestinal side effect profile, have been found in recent studies to retain the haematopoiesisstimulating effects of classical NSAIDs. These results suggest that the indication spectrum of selective COX-2 inhibitors may be extended to the indication of myelosuppression of various etiology. Combining the anti-tumour and haematopoiesis-stimulating activities in a single COX-2 inhibitor may have a positive clinical impact.

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“…The radiotherapy (RT) alters cellular homeostasis, modifying signal transduction pathways and the disposition to apoptosis (4). The acute toxicity of radiation is mediated by local inflammatory phenomena (5) and involves cytokines that are implicated in the cachexia-anorexia syndrome (6), such as interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α. Radiation also generates reactive oxygen species (ROS) by transferring energy to certain cellular components, followed by molecular changes, with damage to lipids, proteins and DNA.…”

Section: Introductionmentioning

confidence: 99%

Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients

et al. 2013

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Abstract. Malnutrition affects 40-50% of patients with ear, nose and throat (ENT) cancer. The aim of this study was to assess changes induced by a specific nutritional supplement enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes, as compared with a standard nutritional supplement, on markers of inflammation, oxidative stress and metabolic status of ENT cancer patients undergoing radiotherapy (RT). Fourteen days after starting RT, 26 patients were randomly allocated to one of two groups, 13 supplemented with Prosure ® , an oncologic formula enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes (specific supplement), and 13 supplemented with Standard-Isosource ® (standard supplement). Patients were evaluated before RT, and 14, 28 and 90 days after starting RT. The results showed that there were no significant differences between the groups, but greater changes were observed in the standard supplement group, such as a decline in body mass index (BMI), reductions in hematocrit, erythrocyte, eosinophil and albumin levels, and a rise in creatinine and urea levels. We concluded that metabolic, inflammatory and oxidative stress parameters were altered during RT, and began to normalize at the end of the study. Patients supplemented with Prosure showed an earlier normalization of these parameters, with more favorable changes in oxidative stress markers and a more balanced evolution, although the difference was not significant.

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On Radiation Damage to Normal Tissues and its Treatment: II. Anti-inflammatory drugs

Cited by 95 publications

References 218 publications

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

Neuroprotective Effect of Eicosapentaenoic Acid in Hippocampus of Rats Exposed to γ-Irradiation

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

Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients

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