PMID- 23010607 OWN - NLM STAT- MEDLINE DCOM- 20130301 LR - 20191210 IS - 0027-5107 (Print) IS - 0027-5107 (Linking) VI - 749 IP - 1-2 DP - 2012 Dec 12 TI - Attenuation of oxidative damage and inflammatory responses by apigenin given to mice after irradiation. PG - 29-38 LID - S1383-5718(12)00268-9 [pii] LID - 10.1016/j.mrgentox.2012.08.001 [doi] AB - We determined the in vivo efficacy of apigenin, as an anti-oxidant and anti-inflammatory agent, given to mice after irradiation. Various concentrations of apigenin (0, 10, 20, and 40mg/kg body weight) were administered to mice by a single intraperitoneal injection 3hr after receiving 0 or 3Gy of (137)Cs gamma rays. Mice receiving vehicle only (no radiation and no apigenin) served as sham controls. We assessed the anti-oxidative activity of apigenin in vivo by measuring levels of 8-hydroxy-2-deoxy guanosine (8-OH-dG) in bone marrow (BM) cells, collected at days 3 and 10 after irradiation, from groups of mice (5 mice per treatment group) with or without apigenin treatment. Simultaneously, we evaluated the ability of apigenin to diminish radiation-induced inflammatory responses in bone-marrow-derived macrophages (BMDMs) from the same individual mice used for measuring the level of 8-OH-dG. To do this, the levels of activated nuclear factor-kappa B (NF-kappa B) and NF-kappa B-regulated pro-inflammatory cytokines [i.e. interleukin 1-beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha)] were measured in BMDMs. Our results indicated significant reductions (p<0.01 or <0.05) in the levels of 8-OH-dG in BM cells collected at both harvest times from irradiated mice receiving apigenin treatment, at all apigenin concentrations tested. Likewise, activation of NF-kappa B in BMDMs collected from gamma-irradiated mice that received apigenin was suppressed at both harvest times. Further, the levels of pro-inflammatory cytokines in gamma-irradiated mice treated with 20 or 40mg/kg body weight apigenin were significantly lower than those in mice receiving radiation only (p<0.01 or <0.05) even at day 10 post-irradiation. Additionally, the ratio of neutrophils to lymphocytes indicated that apigenin ameliorated radiation-induced hematological toxicity. Our study is the first to demonstrate the mitigative/therapeutic effects of apigenin given to mice after irradiation. CI - Copyright (c) 2012 Elsevier B.V. All rights reserved. FAU - Rithidech, Kanokporn Noy AU - Rithidech KN AD - Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691, USA. Kanokporn.Rithidech@sbumed.org FAU - Tungjai, Montree AU - Tungjai M FAU - Reungpatthanaphong, Paiboon AU - Reungpatthanaphong P FAU - Honikel, Louise AU - Honikel L FAU - Simon, Sanford R AU - Simon SR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20120815 PL - Netherlands TA - Mutat Res JT - Mutation research JID - 0400763 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (NF-kappa B) RN - 7V515PI7F6 (Apigenin) RN - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) RN - G9481N71RO (Deoxyguanosine) SB - IM MH - 8-Hydroxy-2'-Deoxyguanosine MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/*pharmacology MH - Apigenin/*pharmacology MH - Bone Marrow Cells/metabolism MH - DNA Damage/drug effects MH - Deoxyguanosine/analogs & derivatives/metabolism MH - Gamma Rays/*adverse effects MH - Inflammation MH - Macrophages/metabolism MH - Mice MH - NF-kappa B/metabolism MH - Oxidative Stress/drug effects EDAT- 2012/09/27 06:00 MHDA- 2013/03/02 06:00 CRDT- 2012/09/27 06:00 PHST- 2012/07/05 00:00 [received] PHST- 2012/08/03 00:00 [revised] PHST- 2012/08/04 00:00 [accepted] PHST- 2012/09/27 06:00 [entrez] PHST- 2012/09/27 06:00 [pubmed] PHST- 2013/03/02 06:00 [medline] AID - S1383-5718(12)00268-9 [pii] AID - 10.1016/j.mrgentox.2012.08.001 [doi] PST - ppublish SO - Mutat Res. 2012 Dec 12;749(1-2):29-38. doi: 10.1016/j.mrgentox.2012.08.001. Epub 2012 Aug 15.