Hydroxylated fullerene: a potential antiinflammatory and antioxidant agent for preventing mouse preterm birth

Objective Intrauterine infection such as by Escherichia coli and Ureaplasma spp induce placental inflammation and are one of the leading causes of preterm birth. Here we evaluated hydroxylated fullerene (C 60 [OH] 44 ) for its in vitro antiinflammatory and antioxidant effects against host cellular responses to the ureaplasma toll-like receptor 2 (TLR2) ligand, UPM-1. In addition, we investigated the preventative effects of C 60 (OH) 44 in vivo in a mouse preterm birth model that used UPM-1. Study Design TLR2-overexpressing cell lines and the primary cultures of mouse peritoneal macrophages were pretreated with C 60 (OH) 44 . After UPM-1 addition to the cell lines, the activation of the nuclear factor kappa-light chain-enhancer of activated B cells (NF-kappaB) signaling cascade and the production of reactive oxygen species were monitored. The levels of expression of inflammatory cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and the production of reactive oxygen species were quantified after stimulation with UPM-1. The in vivo preventative effects of C 60 (OH) 44 on mice preterm birth were evaluated by analyzing the preterm birth rates and fetal survival rates in the preterm birth mouse model with placental histological analyses. Results Pretreatment with C 60 (OH) 44 significantly suppressed UPM-1-induced NF-kappaB activation and reactive oxygen species production in TLR2-overexpressing cell lines. In the primary culture of mouse peritoneal macrophages, UPM-1-induced production of reactive oxygen species and the expression of inflammatory cytokines such as IL-6, IL-1β, and TNF-α were significantly reduced by pretreatment with C 60 (OH) 44 . In the UPM-1-induced preterm birth mouse model, the preterm birth rate decreased from 72.7% to 18.2% after an injection of C 60 (OH) 44 . Placental examinations of the group injected with C 60 (OH) 44 reduced the damage of the spongiotrophoblast layer and reduced infiltration of neutrophils. Conclusion C 60 (OH) 44 was effective as a preventative agent of preterm birth in mice.