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1.
Nat Nanotechnol ; 6(5): 321-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21460826

RESUMO

The increasing use of nanomaterials has raised concerns about their potential risks to human health. Recent studies have shown that nanoparticles can cross the placenta barrier in pregnant mice and cause neurotoxicity in their offspring, but a more detailed understanding of the effects of nanoparticles on pregnant animals remains elusive. Here, we show that silica and titanium dioxide nanoparticles with diameters of 70 nm and 35 nm, respectively, can cause pregnancy complications when injected intravenously into pregnant mice. The silica and titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain. Mice treated with these nanoparticles had smaller uteri and smaller fetuses than untreated controls. Fullerene molecules and larger (300 and 1,000 nm) silica particles did not induce these complications. These detrimental effects are linked to structural and functional abnormalities in the placenta on the maternal side, and are abolished when the surfaces of the silica nanoparticles are modified with carboxyl and amine groups.


Assuntos
Feto/efeitos dos fármacos , Nanopartículas/toxicidade , Placenta/efeitos dos fármacos , Complicações na Gravidez/induzido quimicamente , Reprodução/efeitos dos fármacos , Animais , Apoptose , Feminino , Feto/patologia , Humanos , Troca Materno-Fetal , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Placenta/patologia , Gravidez , Dióxido de Silício , Titânio
2.
Arthritis Rheum ; 56(10): 3307-18, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17907184

RESUMO

OBJECTIVE: Studies have shown the roles of oxidative stress in the pathogenesis of osteoarthritis (OA) and induction of chondrocyte senescence during OA progression. The aim of this study was to examine the potential of a strong free-radical scavenger, water-soluble fullerene (C60), as a protective agent against catabolic stress-induced degeneration of articular cartilage in OA, both in vitro and in vivo. METHODS: In the presence or absence of C60 (100 microM), human chondrocytes were incubated with interleukin-1beta (10 ng/ml) or H2O2 (100 microM), and chondrocyte activity was analyzed. An animal model of OA was produced in rabbits by resection of the medial meniscus and medial collateral ligament. Rabbits were divided into 5 subgroups: sham operation or treatment with C60 at 0.1 microM, 1 microM, 10 microM, or 40 microM. The left knee joint was injected intraarticularly with water-soluble C60 (2 ml), while, as a control, the right knee joint received 50% polyethylene glycol (2 ml), once weekly for 4 weeks or 8 weeks. Knee bone and cartilage tissue were prepared for histologic analysis. In addition, in the OA rabbit model, the effect of C60 (10 microM) on degeneration of articular cartilage was compared with that of sodium hyaluronate (HA) (5 mg/ml). RESULTS: C60 (100 microM) inhibited the catabolic stress-induced production of matrix-degrading enzymes (matrix metalloproteinases 1, 3, and 13), down-regulation of matrix production, and apoptosis and premature senescence in human chondrocytes in vitro. In rabbits with OA, treatment with water-soluble C60 significantly reduced articular cartilage degeneration, whereas control knee joints showed progression of cartilage degeneration with time. This inhibitory effect was dose dependent, and was superior to that of HA. Combined treatment with C60 and HA yielded a significant reduction in cartilage degeneration compared with either treatment alone. CONCLUSION: The results indicate that C60 fullerene is a potential therapeutic agent for the protection of articular cartilage against progression of OA.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Fulerenos/farmacologia , Osteoartrite do Joelho/terapia , Adjuvantes Imunológicos/farmacologia , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Cartilagem Articular/metabolismo , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Condrócitos/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Regulação para Baixo , Humanos , Ácido Hialurônico/farmacologia , Técnicas In Vitro , Osteoartrite do Joelho/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coelhos
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