Fullerene-based antioxidants and neurodegenerative disorders

Dugan, Laura L.; Lovett, E.G.; Quick, Kevin L.; Lotharius, Julie; Lin, Tien‐Sung; O’Malley, Karen L.

doi:10.1016/s1353-8020(00)00064-x

Cited by 305 publications

(168 citation statements)

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“…Several studies have demonstrated that C60, as a therapeutic antioxidant, works significantly better than other natural and synthetic antioxidants in degenerative diseases (36)(37)(38)(39)(40). It has been reported that carboxyfullerene protects human keratinocytes from apoptosis induced by exposure to oxidative stress (40).…”

Section: Discussionmentioning

confidence: 99%

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Water‐soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down‐regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development

Yudoh

Shishido

Murayama

et al. 2007

Arthritis & Rheumatism

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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, watersoluble 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 M), human chondrocytes were incubated with interleukin-1␤ (10 ng/ml) or H 2 O 2 (100 M), 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 M, 1 M, 10 M, or 40 M. The left knee joint was injected intraarticularly with watersoluble 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 M) on degeneration of articular cartilage was compared with that of sodium hyaluronate (HA) (5 mg/ml).Results. C60 (100 M) inhibited the catabolic stress-induced production of matrix-degrading enzymes (matrix metalloproteinases 1, 3, and 13), downregulation 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.During the development of osteoarthritis (OA), mechanical and chemical stresses on articular cartilage change the stable cellular activities of chondrocytes and stimulate the production of growth factors and matrix proteins as well as inflammation mediators (1-4). It is well known that catabolic-stressed chondrocytes produce excess amounts of reactive oxygen species (ROS) (superoxide, nitric oxide, hydrogen peroxide, and peroxynitrite) as well as proinflammatory cytokines and chemokines (4-9).Studies have provided ample confirmation of the generation of ROS and the depletion of cellular antioxidants in degenerated articular cartilage (8-10). Numerous reports have indicated that the degeneration of articular cartilage is partially mediated by oxygenderived free radicals (8-12). Kurz et al reported that the extent of mechanical stress on articular cartilage is sufficient to stimulate an excess production of ROS from chondrocytes, leading to depolymerization of hyaluronic acid and chondrocyte death (11,12). Similarly, Gree...

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Section: Discussionmentioning

confidence: 99%

“…In addition, fullerene inhibits neuronal apoptosis by scavenging ROS (39), and protects human skin keratinocytes from ROS-induced cell death after ultraviolet stress (40). These findings suggest that fullerene is a useful agent in protecting against the oxygen-derived free radical-induced pathologic features in a variety of diseases (41).…”

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confidence: 94%

Water‐soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down‐regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development

Yudoh

Shishido

Murayama

et al. 2007

Arthritis & Rheumatism

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“…The effects are dependent on the structural characteristics; the polyhydroxy fullerenes are the most potent scavengers. Protective effects in neurodegenerative diseases were reported in a mouse model of familial amyotrophic lateral sclerosis and in Parkinson's disease (97). Robust neuropro-…”

Section: Nonmetal-based Sod Mimicsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

459

680

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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“…Specifically, polyhydroxylated C 60 fullerenol was shown to inhibit glutamate receptors, which can further induce elevation of intracellular calcium and lead to reduction of neuronal toxicity (Jin et al 2000). Furthermore, a water-soluble carboxyfullerene, malonic acid C 60 derivative exhibited neuroprotective effects in vitro by limiting excitotoxicity (Dugan et al 1997) and apoptosis of cultured cortical neurons and in vivo by delaying the onset of motor degeneration in a mouse model of familial amyotrophic lateral sclerosis (Dugan et al 2001). In another study, fullerene C 60 core was modified with a layer of malonate ester dendrimers, which increased solubility and reactive surface area of the nanoparticles.…”

Section: Nanomaterials For Neuroprotectionmentioning

confidence: 99%

Novel Nanomaterials for Clinical Neuroscience

Gilmore

Xiang

Quan

et al. 2008

J Neuroimmune Pharmacol

201

118

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Neurodegenerative disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population ages. The field of nanomedicine is rapidly expanding and promises revolutionary advances to the diagnosis and treatment of devastating human diseases. This paper provides an overview of novel nanomaterials that have potential to improve diagnosis and therapy of neurodegenerative disorders. Examples include liposomes, nanoparticles, polymeric micelles, block ionomer complexes, nanogels, and dendrimers that have been tested clinically or in experimental models for delivery of drugs, genes, and imaging agents. More recently discovered nanotubes and nanofibers are evaluated as promising scaffolds for neuroregeneration. Novel experimental neuroprotective strategies also include nanomaterials, such as fullerenes, which have antioxidant properties to eliminate reactive oxygen species in the brain to mitigate oxidative stress. Novel technologies to enable these materials to cross the blood brain barrier will allow efficient systemic delivery of therapeutic and diagnostic agents to the brain. Furthermore, by combining such nanomaterials with cell-based delivery strategies, the outcomes of neurodegenerative disorders can be greatly improved.

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Fullerene-based antioxidants and neurodegenerative disorders

Cited by 305 publications

References 9 publications

Water‐soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down‐regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development

Water‐soluble C60 fullerene prevents degeneration of articular cartilage in osteoarthritis via down‐regulation of chondrocyte catabolic activity and inhibition of cartilage degeneration during disease development

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Novel Nanomaterials for Clinical Neuroscience

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