Amifostine Reduces Radiation-Induced Complications in a Murine Model of Expander-Based Breast Reconstruction

Felice, Peter A.; Nelson, Noah S.; Page, Erin E.; Deshpande, Sagar S.; Donneys, Alexis; Rodrı́guez, José J.; Buchman, Steven R.

doi:10.1097/prs.0000000000000543

Cited by 14 publications

(19 citation statements)

References 15 publications

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“…At present, Androstenediol, OrbeShield ™ , BIO 300, CBLB502, HemaMax ™ and Ex-RAD are some potential radioprotectors which are under Investigational New Drug (IND) status, but require further investigation to be approved by the US Food and Drug Administration (FDA). Although a number of potential drug candidates have been shown to be radioprotective in animal models, most cause significant side effects and are still under pre-clinical or clinical evaluation [ 2 , 11 , 24 , 27 – 30 ]. For example, Amifostine is FDA-approved to treat xerostomia (dryness of mouth) after head and neck radiotherapy, but it commonly is accompanied with side effects such as nausea, vomiting, chills, fever, dizziness, hypotension and skin rashes [ 27 , 31 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although a number of potential drug candidates have been shown to be radioprotective in animal models, most cause significant side effects and are still under pre-clinical or clinical evaluation [ 2 , 11 , 24 , 27 – 30 ]. For example, Amifostine is FDA-approved to treat xerostomia (dryness of mouth) after head and neck radiotherapy, but it commonly is accompanied with side effects such as nausea, vomiting, chills, fever, dizziness, hypotension and skin rashes [ 27 , 31 – 34 ]. NEUPOGEN ® (filgrastim) and NEULASTA ® (pegfilgrastim), recently approved by the FDA to treat acute hematopoietic syndrome and neutropenia, respectively, also cause side effects such as bone pain and pain in extremities coupled with other risks such as fatal splenic rupture, acute respiratory distress syndrome, fatal sickle cell crisis, serious allergic reactions, and glomerulonephritis [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

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MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation

Gupta

Gayen

Smith³

et al. 2016

PLoS ONE

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The radioprotective capacity of a rationally-designed Mn2+-decapeptide complex (MDP), based on Mn antioxidants in the bacterium Deinococcus radiodurans, was investigated in a mouse model of radiation injury. MDP was previously reported to be extraordinarily radioprotective of proteins in the setting of vaccine development. The peptide-component (DEHGTAVMLK) of MDP applied here was selected from a group of synthetic peptides screened in vitro for their ability to protect cultured human cells and purified enzymes from extreme damage caused by ionizing radiation (IR). We show that the peptides accumulated in Jurkat T-cells and protected them from 100 Gy. MDP preserved the activity of T4 DNA ligase exposed to 60,000 Gy. In vivo, MDP was nontoxic and protected B6D2F1/J (female) mice from acute radiation syndrome. All irradiated mice treated with MDP survived exposure to 9.5 Gy (LD70/30) in comparison to the untreated mice, which displayed 63% lethality after 30 days. Our results show that MDP provides early protection of white blood cells, and attenuates IR-induced damage to bone marrow and hematopoietic stem cells via G-CSF and GM-CSF modulation. Moreover, MDP mediated the immunomodulation of several cytokine concentrations in serum including G-CSF, GM-CSF, IL-3 and IL-10 during early recovery. Our results present the necessary prelude for future efforts towards clinical application of MDP as a promising IR countermeasure. Further investigation of MDP as a pre-exposure prophylactic and post-exposure therapeutic in radiotherapy and radiation emergencies is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation

Gupta

Gayen

Smith³

et al. 2016

PLoS ONE

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“…The protective effects of amifostine on different radiation types and doses in acute period were studied in recent literature, but there are no study evaluating effects of amifostine on bacterial overgrowth and translocation after acute radiation enteritis [12][13][14] . In our study, the effects of amifostine on both bacterial translocation and bacterial overgrowth in colonic flora after acute radiation enteritis were evaluated in a rat model.…”

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confidence: 99%

The effect of amifostine on bacterial translocation after radiation ınduced acute enteritis

et al. 2016

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PURPOSE:To investigate the effects of amifostine on bacterial translocation and overgrowth in colonic flora after acute radiation enteritis in a rat model. METHODS:Thirty-two female Wistar albino rats were divided into four groups: Group-1 (n=8): only normal saline was administered intraperitoneally. Group-2 (n=8): first serum saline was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. Group-3 (n=8): only amifostine 200 ml/kg was administered intraperitoneally and radiation was not applied.Group-4 (n=8): first amifostine 200 ml/kg was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. On the 5th day after radiation, samples of mesenteric lymph tissues and cecal contents were taken by laparotomy for microbiological culture. RESULTS:Intraperitoneal amifostine administration significantly decreased the bacterial overgrowth related to radiation in colon but did not significantly decrease the bacterial translocation. CONCLUSİON:Although not providing a full protection on the damaged mucosal barrier, amifostine significantly decreased the bacterial overgrowth in the cecal content after high dose radiation. There is a need to find out appropriate amifostine dose under different radiation applications avoiding bacterial translocation in gastrointestinal system.

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“…Amifostine is a common used radioprotector drug, approved by the United States Food and Drug Administration (FDA). At present, amifostine is mainly used in reducing the side effects induced by radiation therapy in the patients with malignant tumors [ 27 ]. In an in vivo study, Merter et al found that amifostine could attenuate ischemia/reperfusion injury of monkey kidneys by increasing intracellular GSH level [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

SOD2 Mediates Amifostine‐Induced Protection against Glutamate in PC12 Cells

Jia

Zhang

Shi

et al. 2015

Oxidative Medicine and Cellular Longevity

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Background. Cytoprotectant amifostine attenuates radiation-induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells. Methods. PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular Cu/Zn SOD (SOD1) and SOD2 activities; western blot analysis and immunofluorescence staining were performed to investigate SOD2 protein expression; MTT, lactate dehydrogenase (LDH), release and cell morphology were used to evaluate cell injury degree, and apoptotic rate and cleaved caspase-3 expression were taken to assess apoptosis; mitochondrial superoxide production, intracellular reactive oxygen species (ROS), and glutathione (GSH) and catalase (CAT) levels were evaluated by reagent kits. Results. Amifostine increased SOD2 activity and expression, decreased cell injury and apoptosis, reduced mitochondrial superoxide production and intracellular ROS generation, and restored intracellular GSH and CAT levels in PC12 cells exposed to glutamate. SOD2-siRNA, however, significantly reversed the amifostine-induced cytoprotective and antioxidative actions. Conclusion. SOD2 mediates amifostine-induced protection in PC12 cells exposed to glutamate.

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Amifostine Reduces Radiation-Induced Complications in a Murine Model of Expander-Based Breast Reconstruction

Cited by 14 publications

References 15 publications

MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation

MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation

The effect of amifostine on bacterial translocation after radiation ınduced acute enteritis

SOD2 Mediates Amifostine‐Induced Protection against Glutamate in PC12 Cells

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