Radioprotection of mouse skin by WR-2721 in single and fractionated treatments

Stewart, Fiona; Rojas, Á.

doi:10.1259/0007-1285-55-649-42

Cited by 42 publications

(3 citation statements)

References 21 publications

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“…In long-term studies, Am has a radiation dose modification factor (DMF) greater than 2, meaning that a 15-Gy salivary gland dose can be mitigated to an equivalent of <7.5 Gy (Sodicoff et al 1978). DMF is a function of amifostine concentration, which we have maximized through local delivery (Stewart and Rojas 1982). It has been shown that saliva flow from the rat SMG at 3 mo following doses <7.5 Gy is not significantly lower than baseline (Nagler et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

et al. 2018

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Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.

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Section: Discussionmentioning

confidence: 99%

Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

et al. 2018

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“…Yuhas and Storer [4] subsequently showed that pretreatment with amifostine effectively protects normal tissues from the toxicities of therapeutic radiation without protecting tumors. Amifostine was shown to protect irradiated gastrointestinal mucosal tissue [5], parotid gland [6,7,8,9], kidney [10], bone marrow [11], spermatogenetic cells [12,13], skin [14], hair follicles [15] and lung [16] in mice.…”

Section: Introductionmentioning

confidence: 99%

In vivo Study to Evaluate the Protective Effects of Amifostine on Radiation-Induced Damage of Testis Tissue

et al. 2005

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Objective: To investigate the early protective effects of amifostine against radiation-induced damage on rat testis tissue. Methods: Eighty adult male Wistar rats were randomized to 4 groups: Saline solution was given to group A for control, 200 mg/kg amifostine (WR-2721) to group B, a single fraction of 6 Gy local irradiation to testes in group C and 200 mg/kg amifostine 15–30 min before 6 Gy testicular irradiation to group D. Animals were sacrificed 3 weeks after treatment and their testes were removed for macroscopic, microscopic and ultrastructural histopathological examination. Results: The weights, widths and lengths of testes in the last 3 groups had decreased significantly when compared with the control group, but the decrease in widths after irradiation was found to be significantly less only in the amifostine plus radiation group. There was a significant reduction of testis weights in relation to the individual body weights in the irradiated testes compared with the other groups (p < 0.005), while there was no significant change of testis weight/total body weight ratio in amifostine plus irradiation group. Spermatogonium A and primary spermatocyte counts were also less in the treatment groups, and primary spermatocyte numbers were significantly higher in amifostine plus radiation group when compared with radiation alone group (p < 0.005). Pretreatment with amifostine reduced the decrease of primary spermatocyte counts by a factor of 1.28. Electron microscopic analysis did not show any cytotoxic effect of amifostine alone, and furthermore, ultrastructural findings were normal with the addition of amifostine prior to irradiation, though there was damage in the radiation exposure group. Conclusion: Amifostine when given alone by itself appears to cause adverse alterations in testis tissue; however, it has a radioprotective effect on spermiogenetic cells when used prior to radiation.

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“…5-hydroxytryptamine, catecholamine and acetylcholine (24,25,42,8,59,60,37,38,6,57). Studies on the chemical protection of the brain in terms of DNA, RNA and protein contents against ionizing radiation have received little attention (11,51,32,39).…”

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confidence: 99%

Effect of Two Graded Doses of Whole-Body X-Irradiation and Radioprotection by the Use of S-Phenethyl Formamidino 4 (N-Ethyl Isothioamide) Morpholine Dihydrochloride

Ss¹,

Pk²,

Sn³

1983

Nuklearmedizin

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The protection offered by a newly synthesized compound (S-phenethyl-formamidino-4(N-ethyl isothioamide) morpholine dihydrochloride) against radiation effects on DNA, RNA and protein biosynthetic processes in the brain, and on metabolites of 5-HT and nor-adrenalin, i.e., 5-HIAA and VMA, in the urine, including the radiobiological damage to thyroid and testes, was evaluated. The use of the compound prior to irradiation prevented radiation-induced changes in the thyroid and testes. The radiation-induced alterations in the pattern of DNA, RNA, protein in the brain, and in 5-HIAA and VMA in urine could be averted by treatment with this compound prior to each dose of X-irradiation.

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Radioprotection of mouse skin by WR-2721 in single and fractionated treatments

Cited by 42 publications

References 21 publications

Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

In vivo Study to Evaluate the Protective Effects of Amifostine on Radiation-Induced Damage of Testis Tissue

Effect of Two Graded Doses of Whole-Body X-Irradiation and Radioprotection by the Use of S-Phenethyl Formamidino 4 (N-Ethyl Isothioamide) Morpholine Dihydrochloride

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