title: Redox maintenance and concerted modulation of gene expression and signaling pathways by a nanoformulation of curcumin protects peripheral blood mononuclear cells against gamma radiation.
abstract: Exposure to ionizing radiation (IR) could be detrimental to health. Oxidative stress, DNA damage, and inflammation are implicated in radiation damage. Curcumin, a natural polyphenol, has remarkable antioxidant, anti-inflammation and anticarcinogenic properties and is reported to protect cells and organisms against gamma-rays. We have recently enhanced solubility of curcumin via a novel dendrosomal nanoformulation (DNC). The objective of this study was to assess the potential efficacy of this nanoformulation in protecting human peripheral blood mononuclear cells (PBMC) against gamma-radiation. IR-induced damage was evident in reactive oxygen species, antioxidant enzymes activities, glutathione, lipid peroxidation, and viability assays. Treatment by DNC, showing superiority to curcumin, effectively counteracted these effects and reduced DNA damage as determined via 8-OHdG levels and lipid peroxidation as measured by the level of TBARS (as well as lipid hydroperoxides and 8-isoprostane). PBMC pretreatment by DNC prior to irradiation proved effective as well. Uptake kinetics revealed enhanced uptake of DNC compared to curcumin, particularly after irradiation. DNC suppressed IR-induced NF-κB activation 18 h post-irradiation. It induced Nrf2 binding activity early after irradiation which was sustained to 18 h. Gene expression analysis of a chosen set of radiation response genes in irradiated PBMC revealed a similar profile for DNA damage response and repair genes including FDXR, XPC, DDB2, and GADD45 in DNC-treated cells compared to IR control. However, in response to radiation, an altered profile of expression was noticed for CDKN1A (p21), MDM2, IFNG, and BBC3 (PUMA) genes after DNC treatment.
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran. Electronic address: behroozsoltani@gmail.com.
authors.forename: Behrooz
authors.initials: B
authors.lastname: Soltani
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran; School of Chemistry, College of Science, University of Tehran, Tehran, Iran. Electronic address: nasser.ghaemi@khayam.ut.ac.ir.
authors.forename: Nasser
authors.initials: N
authors.lastname: Ghaemi
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: sadeghma@modares.ac.ir.
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.affiliation: Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran. Electronic address: fnajafi@icrc.ac.ir.
authors.forename: Farhood
authors.initials: F
authors.lastname: Najafi
mesh_terms: D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000235:genetics; D050091:Dendrimers / Q000493:pharmacokinetics; D005720:Gamma Rays / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D010084:Oxidation-Reduction / Q000187:drug effects* / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D050091:Dendrimers; D011837:Radiation-Protective Agents; D003474:Curcumin
keywords: BBC3; Curcumin; Nano; Nrf2; Peripheral blood; Radiation