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Metabolomic Studies in Tissues of Mice Treated With Amifostine and Exposed to Gamma-Radiation

Metabolomic Studies in Tissues of Mice Treated With Amifostine and Exposed to Gamma-Radiation

Amrita K Cheema, Yaoxiang Li, Michael Girgis, Meth Jayatilake, Madison Simas, Stephen Y Wise, Ayodele O Olabisi, Thomas M Seed, Vijay K Singh

Sci Rep. 2019 Oct 30;9(1):15701.

PMID: 31666611

Abstract:

Although multiple radioprotectors are currently being investigated preclinically for efficacy and safety, few studies have investigated concomitant metabolic changes. This study examines the effects of amifostine on the metabolic profiles in tissues of mice exposed to cobalt-60 total-body gamma-radiation. Global metabolomic and lipidomic changes were analyzed using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in bone marrow, jejunum, and lung samples of amifostine-treated and saline-treated control mice. Results demonstrate that radiation exposure leads to tissue specific metabolic responses that were corrected in part by treatment with amifostine in a drug-dose dependent manner. Bone marrow exhibited robust responses to radiation and was also highly responsive to protective effects of amifostine, while jejunum and lung showed only modest changes. Treatment with amifostine at 200 mg/kg prior to irradiation seemed to impart maximum survival benefit, while the lower dose of 50 mg/kg offered only limited survival benefit. These findings show that the administration of amifostine causes metabolic shifts that would provide an overall benefit to radiation injury and underscore the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of amifostine. This approach may be helpful in identifying biomarkers for radioprotective efficacy of amifostine and other countermeasures under development.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP112901685-A	Amifostine		112901-68-5	Price

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