|Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent.|
|PMID: 22523285 Owner: NLM Status: MEDLINE|
|BACKGROUND: Carbamazepine, a sodium channel blocker and pro-autophagy agent used in the treatment of epilepsy and trigeminal neuralgia, is also an ionizing radiation mitigator and protector.
MATERIALS AND METHODS: We measured the effect of carbamazepine, compared to other pro-autophagy drugs (i.e. lithium and valproic acid), on irradiation of autophagy incompetent (Atg5(-/-)) and competent (Atg5(+/+)) mouse embryonic fibroblasts, p53(-/-) and p53(+/+) bone marrow stromal cells, and human IB3, KM101, HeLa, and umbilical cord blood cell and in total body-irradiated or orthotopic tumor-bearing mice.
RESULTS: Carbamazepine, but not other pro-autophagy drugs, was a radiation protector and mitigator for mouse cell lines, independent of apoptosis, autophagy, p53, antioxidant store depletion, and class I phosphatidylinositol 3-kinase, but was ineffective with human cells. Carbamazepine was effective when delivered 24 hours before or 12 hours after total body irradiation of C57BL/6HNsd mice and did not protect orthotopic Lewis lung tumors.
CONCLUSION: Carbamazepine is a murine radiation protector and mitigator.
|Hyun Kim; Mark E Bernard; Amy Farkas; Julie Goff; Ronny Kalash; Frank Houghton; Donna Shields; Darcy Franicola; Tracy Dixon; Xichen Zhang; Michael Epperly; Hong Wang; Murat Can Cobanoglu; Joel S Greenberger|
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|Type: Journal Article; Research Support, N.I.H., Extramural|
|Title: In vivo (Athens, Greece) Volume: 26 ISSN: 1791-7549 ISO Abbreviation: In Vivo Publication Date: 2012 May-Jun|
|Created Date: 2012-04-23 Completed Date: 2012-08-13 Revised Date: 2014-09-24|
Medline Journal Info:
|Nlm Unique ID: 8806809 Medline TA: In Vivo Country: Greece|
|Languages: eng Pagination: 341-54 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Antioxidants / metabolism
Apoptosis / drug effects, radiation effects
Autophagy / drug effects*, radiation effects
Carbamazepine / pharmacology*, therapeutic use
Carcinoma, Lewis Lung / drug therapy, pathology, radiotherapy
Cell Line, Tumor
Cell Survival / drug effects, radiation effects
Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors, metabolism
Fetal Blood / cytology
Fibroblasts / drug effects, metabolism, radiation effects
Gene Knockout Techniques
Hematopoietic Stem Cells / drug effects, radiation effects
Lithium Chloride / pharmacology
Membrane Potential, Mitochondrial / drug effects
Mice, Inbred C57BL
Microtubule-Associated Proteins / genetics, metabolism
Radiation-Protective Agents / pharmacology*, therapeutic use
Tumor Burden / drug effects, radiation effects
Tumor Suppressor Protein p53 / metabolism*
Valproic Acid / pharmacology
|T32 AG021885-10/AG/NIA NIH HHS; T32AG21885/AG/NIA NIH HHS; U19 AI068021/AI/NIAID NIH HHS; U19 AI068021-08/AI/NIAID NIH HHS; U19A1068021//PHS HHS|
|0/Antioxidants; 0/Atg5 protein, mouse; 0/Microtubule-Associated Proteins; 0/Radiation-Protective Agents; 0/Tumor Suppressor Protein p53; 33CM23913M/Carbamazepine; 614OI1Z5WI/Valproic Acid; EC 22.214.171.124/Class I Phosphatidylinositol 3-Kinases; G4962QA067/Lithium Chloride|
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