title: 1,4-Naphthoquinone, a pro-oxidant, ameliorated radiation induced gastro-intestinal injury through perturbation of cellular redox and activation of Nrf2 pathway.
abstract: Detrimental effects of ionizing radiation (IR) are observed at the doses above 1 Gy. Treatment modalities are available up to doses of 6 Gy including bonemarrow transplantation and administration of antibiotics. However, exposure to IR doses above 8 Gy results in gastro-intestinal (GI) syndrome characterised by denudated villi, apoptosis of crypt cells and elevated inflammatory responses. Multiple strategies have been employed to investigate novel agents to protect against IR induced injury. Since cellular redox homeostasis plays a pivotal role in deciding the cell fate, present study was undertaken to explore the potential of 1,4-naphthoquinone (NQ), a pro-oxidant, to ameliorate IR induced GI syndrome. NQ protected INT 407 cells against IR induced cell death of intestinal epithelial cells in vitro. NQ induced perturbation in cellular redox status and induced the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. Thiol antioxidant and inhibitors of Nrf2 pathway abrogated the radioprotection offered by NQ. Further, knocking down Nrf2 rescind the NQ mediated protection against IR induced cell death. In conclusion, NQ protects against IR radiation induced GI syndrome in vitro by perturbing cellular redox and activating Nrf2 pathway. This is the first report highlighting the potential of a pro-oxidant to ameliorate IR induced GI injury.
authors.affiliation: Department of Life Sciences, Shri Guru Ram Rai Institute of Technology & Sciences.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000209:etiology; D055785:Gene Knockdown Techniques; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000235:genetics*; D009285:Naphthoquinones / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016877:Oxidants / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009285:Naphthoquinones; D016877:Oxidants; D034741:RNA, Small Interfering; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; D053148:Caspase 3; C035342:1,4-naphthoquinone