title: Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.
abstract: The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Ujjal
authors.initials: U
authors.lastname: Das
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Manna
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Amitava
authors.initials: A
authors.lastname: Khan
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Mahuya
authors.initials: M
authors.lastname: Sinha
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Sushobhan
authors.initials: S
authors.lastname: Biswas
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Aaveri
authors.initials: A
authors.lastname: Sengupta
authors.affiliation: b Division of Radiation Biology , UGC-DAE CSR Center Kolkata , Kolkata , West Bengal , India.
authors.forename: Anindita
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: a Department of Physiology , Centre for Nanoscience and Nanotechnology and Centre with Potential for Excellence in Particular Area (CPEPA), University of Calcutta , Kolkata , West Bengal , India.
authors.forename: Sanjit
authors.initials: S
authors.lastname: Dey
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D003188:Composite Resins; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005720:Gamma Rays; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010851:Picrates / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D001713:Biphenyl Compounds; D003188:Composite Resins; D003373:Coumaric Acids; D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C516055:Nulite F; D010851:Picrates; D011837:Radiation-Protective Agents; C004999:ferulic acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D013482:Superoxide Dismutase
keywords: DNA damage; DNA-PKcs; Ferulic acid; oxidative stress; γ-radiation