Radiation-induced surge of macrophage foam cell formation, oxidative damage, and cytokine release is attenuated by a nanoformulation of curcumin.
We examined the potential of a dendrosomal nanoformulation of curcumin (DNC) for intervention of ionizing radiation (IR)-induced damage (particularly leading to atherosclerosis), employing an irradiated THP-1 macrophage model.



Differentiated THP-1 macrophages were irradiated and treated with curcumin or DNC nanoformulation (and oxidized low density lipoprotein, ox-LDL, to promote foam cells). Chemical, biochemical, and genetics tools including viability and apoptosis, multiple ELISA, real-time PCR, Western blotting, enzyme activity, and fluorimetry assays were employed to illustrate IR damage as well as the DNC intervention potential.



DNC per se at 10 μM exerted no cytotoxic effects on macrophages. However, it caused apoptosis in 2 Gy-irradiated macrophages which were treated with ox-LDL, chiefly through a caspase-dependent pathway involving caspase-3. Concurrently, 10 μM DNC prevented the IR-induced rise in lipid accumulation (72% decrease compared to IR control, p < .0001), dil-oxLDL uptake (78% decrease, p < .005), protein and mRNA expression of cholesterol influx genes, CD36 and SR-A, NF-κB activation (81% less binding activity, p < .001; and lower nuclear presence of p65), cytokine (monocyte chemoattractant protein-1 and interleukin-1β) release, reactive oxygen species (ROS), and oxidative damage to DNA (37% decrease in 8-OHdG, p < .05) and lipids (62% decrease in 8-isoprostane, p < .005). DNC facilitated the uptake of curcumin in irradiated macrophages, increased glutathione peroxidase expression and activity, restored glutathione (GSH) level, and upregulated the expression of a cholesterol efflux gene, ABCA1. Two other antioxidants, resveratrol and N-acetyl cycteine (NAC), could simulate some of the beneficial effects of DNC against IR-induced CD36 expression and lipid accumulation, which were obviated by buthionine sulfoximine (BSO) pre-treatment of macrophages. However, some modulatory effects of DNC, particularly on lipid accumulation and the expression of SR-A and ABCA1 genes, seemed to be independent of its antioxidant effect, since they were still observed in BSO-pretreated macrophages, depleted of GSH.



DNC treatment suppresses IR-induced oxidative damage, inflammation, and foam cell formation in macrophages through multiple mechanisms.
a Department of Biotechnology , College of Science, University of Tehran , Tehran , Iran.
Behrooz
B
Soltani
b Department of Genetics, Faculty of Biological Sciences , Tarbiat Modares University , Tehran , Iran.
Narges
N
Bodaghabadi
a Department of Biotechnology , College of Science, University of Tehran , Tehran , Iran.|c School of Chemistry , College of Science, University of Tehran , Tehran , Iran.
Nasser
N
Ghaemi
b Department of Genetics, Faculty of Biological Sciences , Tarbiat Modares University , Tehran , Iran.
Majid
M
Sadeghizadeh
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry*; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004339:Drug Compounding / Q000379:methods*; D005487:Foam Cells / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry; D018384:Oxidative Stress / Q000276:immunology* / Q000528:radiation effects; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000276:immunology
D016207:Cytokines; D053769:Nanocapsules; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D003474:Curcumin
Apoptosis; GSH; NF-κB; foam cell; radioprotectors; reactive oxygen species