Antioxidant and anti-inflammatory effect of lycopene to be used for the treatment of osteoporosis

Antioxidant and anti-inflammatory effect of lycopene to be used for the treatment of osteoporosis BACKGROUND: Osteoporosis is defined as a skeletal disorder characterized by decreased density of normally mineralized bone, consequently bone fragility occurs mainly due to aging with an alteration of the dynamic balance of bone remodeling, with increased osteoclasts activity and reduce bone formation. The pathogenesis of osteoporosis is related to oxidative stress that increased with aging or in an inflammatory state, in fact, reactive oxygen species (ROS) suppress osteoblast differentiation while promote osteoclast activity. Thus anti-oxidant compounds might have a role in reducing bone loss, to this end we tested lycopene, a carotenoid that inhibits the activation of NF-κB and the release of pro-inflammatory cytokines in an experimental model of osteoblast impairment due to H2O2 stimulation. METHODS: Human fetal osteoblasts hFOB 1.19 (ATCC® CRL-11372™), MC3T3-E1 (ATCC CRL-2594™) and MLO-A5 (Kerafast) were cultured under standard conditions and were stimulated with H2O2 at 300 μM for 6 hours. After stimulation lycopene was added at different doses (0.5, 1 and 2 μM) for up to 24 hours. At the end of the experiment viability assay, Reactive oxygen species (ROS) detection assay, qRT-PCR and Western Blot were performed to evaluate expression of factors involved in inflammation, apoptosis, oxidative stress and osteoblast differentiation. RESULTS: H2O2 reduced the expression of the antioxidant transcription factor NRF2 and increased the pro-inflammatory cytokines. The expression of NRF2 is increased using lycopene as a result of an antioxidant mechanism; H2O2 increased levels of TNF-α, IL-1β, IL-6, Bax and Caspase 3, while lycopene inhibited the H2O2-induced production of these pro-inflammatory cytokines pro-apoptotic factors. Lycopene treatment increased expression of factors involved in osteoblast differentiation. CONCLUSIONS: Osteoporosis is a bone metabolic disease with multifactorial etiopathogenesis, for this reason, despite these preliminary results obtained in vitro, whom suggest that lycopene could play a protective role, certainly in vivo studies are needed to confirm its role in pathology.