title: Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.
abstract: Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss.
authors.affiliation: Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Rethi
authors.initials: R
authors.lastname: Raghu Nadhanan
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Abimosleh
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Su
authors.forename: Michaela A
authors.initials: MA
authors.lastname: Scherer
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Howarth
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001862:Bone Resorption / Q000139:chemically induced* / Q000517:prevention & control*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects; D002364:Caseins / Q000494:pharmacology; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000032:analysis / Q000494:pharmacology*; D019587:Dietary Supplements / Q000032:analysis; D020312:Dromaiidae; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006132:Growth Plate / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D010010:Osteoclasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000964:Antimetabolites, Antineoplastic; D002364:Caseins; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D005472:Fluorouracil