Radioprotection in mice following oral delivery of amifostine nanoparticles

Pamujula, Sarala; Kishore, Vimal; Rider, Barbara J.; Fermin, César D.; Graves, Richard A; Agrawal, Krishna C.; Mandal, Tarun K.

doi:10.1080/09553000500103470

Cited by 41 publications

(33 citation statements)

References 21 publications

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“…Previously, numerous researchers reported finding strong radioprotective action of amifostine when sufficiently high dosing regimens were applied (e.g., > 100 mg/kg) to various experimental animal models of acute injury, using a variety of measured end points (Davidson et al 1980, Fatome et al 1987, Landauer et al 1987, Giambrarresi and Walker 1989, Patchen et al 1990, Weiss et al 1992, Patchen and MacVittie 1994, Mazur 1996, Seed et al 2002a, Srinivasan et al 2002, Stone et al 2004, Pamujula et al 2005). In all of these studies there was positive correlation between amifostine’s hematopoietic tissue sparing effect and survival.…”

Section: Discussionmentioning

confidence: 99%

Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

Seed¹,

Inal²,

Singh

2014

International Journal of Radiation Biology

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PurposeAmifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie?Material and methodsC3H/HEN mice were administered varying doses of amifostine (25–100 mg/kg) 30 min prior to cobalt-60 irradiation and euthanized between 4–14 days for blood and bone marrow collection and analyses.ResultsUnder steady-state, amifostine had little effect on bipotential and multi-potential marrow progenitors but marginally suppressed a more primitive, lineage negative progenitor subpopulation. In irradiated animals, prophylactic drug doses greater than 50 mg/kg resulted in significant regeneration of bipotential progenitors, moderate regeneration of multipotential progenitors, but no significant and consistent regeneration of more primitive progenitors. The low amifostine dose (25 mg/kg) failed to elicit consistent and positive, radioprotective actions on any of the progenitor subtypes.ConclusionsRadioprotective doses for amifostine appear to lie between 25 and 50 mg/kg. Mature, lineage-restricted progenitors appear to be more responsive to the protective effects of low doses of amifostine than the more primitive, multipotential progenitors.

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Section: Discussionmentioning

confidence: 99%

Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

Seed¹,

Inal²,

Singh

2014

International Journal of Radiation Biology

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“…In addition, since both types of mushrooms contained the same amounts of antioxidants, the contribution of antioxidants to radioprotection in this study was ruled out. When compared with published data-black mushrooms were more protective than amifostine (60% survival after 9 Gy delivered at 1 Gy/ min 16 ), and equal to flagellin-derived polypeptide (80% survival after 9 Gy delivered at 2.3 Gy/min 18 ). The increase in radiation dose rate is known to make the cellular repair mechanisms less efficient.…”

Section: Discussionmentioning

confidence: 99%

“…One potential radioprotector that has been studied extensively is amifostine. 16,17 While this drug has some radioprotective efficacy, it also has several undesirable properties, including a relatively low radioprotective capacity, serious side effects such as anaphylaxis, and the need for intravenous administration. In a study conducted by Burdelya et al,.…”

Section: Discussionmentioning

confidence: 99%

Compton Scattering by Internal Shields Based on Melanin-Containing Mushrooms Provides Protection of Gastrointestinal Tract from Ionizing Radiation

Revskaya

Chu

Howell

et al. 2012

Cancer Biotherapy and Radiopharmaceuticals

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There is a need for radioprotectors that protect normal tissues from ionizing radiation in patients receiving high doses of radiation and during nuclear emergencies. We investigated the possibility of creating an efficient oral radioprotector based on the natural pigment melanin that would act as an internal shield and protect the tissues via Compton scattering followed by free radical scavenging. CD-1 mice were fed melanin-containing black edible mushrooms Auricularia auricila-judae before 9 Gy total body irradiation. The location of the mushrooms in the body before irradiation was determined by in vivo fluorescent imaging. Black mushrooms protected 80% of mice from the lethal dose, while control mice or those given melanin-devoid mushrooms died from gastrointestinal syndrome. The crypts of mice given black mushrooms showed less apoptosis and more cell division than those in control mice, and their white blood cell and platelet counts were restored at 45 days to preradiation levels. The role of melanin in radioprotection was proven by the fact that mice given white mushrooms supplemented with melanin survived at the same rate as mice given black mushrooms. The ability of melanincontaining mushrooms to provide remarkable protection against radiation suggests that they could be developed into oral radioprotectors.

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“…Geneistein has also been shown to induce hematopoietic stem cell quiescence followed by reduced senescence of HSPCs in vivo [23,36]. Amifostine, the most important adjuvant in radiotherapy, also acts as an antioxidant and also enhances the survival of HSPC in mice [37][38][39].…”

Section: ϯϭmentioning

confidence: 97%