Gamma tocotrienol, a potent radioprotector, preferentially upregulates expression of anti-apoptotic genes to promote intestinal cell survival

Shubhankar Suman, Kamal Datta, Kushal Chakraborty, Shilpa Kulkarni, Kathryn Doiron, Albert J. Fornace, K. Sree Kumar, Martin Hauer-Jensen, Sanchita P. Ghosh

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Gamma tocotrienol (GT3) has been reported as a potent ameliorator of radiation-induced gastrointestinal (GI) toxicity when administered prophylactically. This study aimed to evaluate the role of GT3 mediated pro- and anti-apoptotic gene regulation in protecting mice from radiation-induced GI damage.Male 10- to 12-weeks-old CD2F1 mice were administered with a single dose of 200. mg/kg of GT3 or equal volume of vehicle (5% Tween-80) 24. h before exposure to 11. Gy of whole-body γ-radiation. Mouse jejunum was surgically removed 4 and 24. h after radiation exposure, and was used for PCR array, histology, immunohistochemistry, and immunoblot analysis.Results were compared among vehicle pre-treated no radiation, vehicle pre-treated irradiated, and GT3 pre-treated irradiated groups. GT3 pretreated irradiated groups, both 4. h and 24. h after radiation, showed greater upregulation of anti-apoptotic gene expression than vehicle pretreated irradiated groups. TUNEL staining and intestinal crypt analysis showed protection of jejunum after GT3 pre-treatment and immunoblot results were supportive of PCR data.Our study demonstrated that GT3-mediated protection of intestinal cells from a GI-toxic dose of radiation occurred via upregulation of antiapoptotic and downregulation of pro-apoptotic factors, both at the transcript as well as at the protein levels.

Original languageEnglish (US)
Pages (from-to)488-496
Number of pages9
JournalFood and Chemical Toxicology
Volume60
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

gamma-tocotrienol
cell viability
Cell Survival
Up-Regulation
Genes
Cells
Radiation
jejunum
Jejunum
mice
genes
intestinal crypts
Gene expression
dosage
Polymerase Chain Reaction
Cytoprotection
Polysorbates
Whole-Body Irradiation
histology
Poisons

Keywords

  • Apoptosis
  • Gamma tocotrienol
  • Gastrointestinal toxicity
  • Radiation
  • Radioprotection

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Gamma tocotrienol, a potent radioprotector, preferentially upregulates expression of anti-apoptotic genes to promote intestinal cell survival. / Suman, Shubhankar; Datta, Kamal; Chakraborty, Kushal; Kulkarni, Shilpa; Doiron, Kathryn; Fornace, Albert J.; Sree Kumar, K.; Hauer-Jensen, Martin; Ghosh, Sanchita P.

In: Food and Chemical Toxicology, Vol. 60, 2013, p. 488-496.

Research output: Contribution to journalArticle

Suman, Shubhankar ; Datta, Kamal ; Chakraborty, Kushal ; Kulkarni, Shilpa ; Doiron, Kathryn ; Fornace, Albert J. ; Sree Kumar, K. ; Hauer-Jensen, Martin ; Ghosh, Sanchita P. / Gamma tocotrienol, a potent radioprotector, preferentially upregulates expression of anti-apoptotic genes to promote intestinal cell survival. In: Food and Chemical Toxicology. 2013 ; Vol. 60. pp. 488-496.
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