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.

Keywords:

• Ferulic acid
• γ-radiation
• oxidative stress
• DNA damage
• DNA-PKcs

Acknowledgements

A Research Fellowship from CSIR-HRDG under grant [09/028(0951)/2015-EMR-I] Government of India, to U.D. is gratefully acknowledged. The authors are thankful to Prof. M. Nandi of SINP, Kolkata for providing necessary irradiation facilities. The authors acknowledge Dr Nabendu S. Chatterjee and Dr Surhita Paul for their editorial comments on manuscripts. Prof. S.D. acknowledges the support of funding by LSRB under grant [DLS/81/48222/LSRB-244/SH&DD/2012], CSIR under grant [23(0024)/12/EMR-II], Coconut Development Board under grant [1345/20011-Tech] and West Bengal DBT under grant [593-BT(Estt)/RD-9/11]; and UGC, Government India for support under CPEPA scheme granted [F. No. 8-2/2008(NS/PE)]; Prof. S.D. acknowledges the support of Department of Science and Technology (DST) for PURSE scheme to the Department of Physiology, University of Calcutta.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.