[60]Fullerene is a Powerful Antioxidant in Vivo with No Acute or Subacute Toxicity

Gharbi, Najla; Pressac, M; Hadchouel, Michelle; Szwarc, H.; Wilson, Stephen R.; Moussa, Fathi

doi:10.1021/nl051866b

Cited by 608 publications

(435 citation statements)

References 45 publications

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“…Data indicate that C 3 localizes in mitochondria, where it replaces MnSOD. A carboxyfullerene protected the liver against carbon tetrachloride intoxication in rats (129). In an osteoarthritis model, a carboxylated C 60 prevented catabolic-stress-induced production of matrix metalloproteinases 1, 3, and 13, downregulation of matrix production, apoptosis, and premature senescence of human chondrocytes (treated with interleukin-1b) in vitro, and degeneration of articular cartilage in vivo, in rabbit knees (349).…”

Section: Nonmetal-based Sod Mimicsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

470

689

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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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Section: Nonmetal-based Sod Mimicsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

470

689

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“…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). Exploitation of fullerene could lead to the development of novel therapeutic strategies in the prevention of both chondrocyte aging and cartilage degeneration.…”

mentioning

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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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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“…1 For example, the pristine C 60 fullerenes as a unique class of carbon allotropes are able to penetrate the cell membrane, 2,3 to exhibit antioxidant properties, 4,5 and, being nontoxic (at least at low concentration), 6 to exert specific health effects (e.g., antibacterial, 7 antitumor, 8 and drug carrier 9 ).…”

Section: ■ Introductionmentioning

confidence: 99%

On the Origin of C₆₀ Fullerene Solubility in Aqueous Solution

et al. 2014

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In this work, we report that the surface hydroxylation of C 60 molecules is the most likely mechanism for pristine C 60 fullerenes/C 60 fullerene aggregate stabilization in water, being independent of the method of C 60 fullerene aqueous solution preparation. ■ INTRODUCTIONNanocarbon materials are used in a wide variety of biomedical applications, including biosensorics, targeted drug delivery, chemotherapy, cellular imaging, and diagnostics. 1 For example, the pristine C 60 fullerenes as a unique class of carbon allotropes are able to penetrate the cell membrane, 2,3 to exhibit antioxidant properties, 4,5 and, being nontoxic (at least at low concentration), 6 to exert specific health effects (e.g., antibacterial, 7 antitumor, 8 and drug carrier 9 ).Biomedical applications require a dispersal of C 60 fullerene in a solvent, with aqueous dispersions being preferred because of biocompatibility, safety, or environmental concerns. Although pristine C 60 fullerenes have extremely low water solubility, they can form stable colloid solutions containing individual C 60 fullerenes as well as C 60 fullerene aggregates (clusters) in water when subjected to extended mixing, sonication, or solvent exchange 10−16 (to be further referred to as a C 60 fullerene aqueous colloid solution (C 60 FAS)). However, the origin of stabilization of such particles in water still remains poorly investigated.At least two approaches have been suggested in order to explain the stability of fullerene particles in water solutions. One of them 17 postulates the formation of a water shell around C 60 molecules stabilized simultaneously by the H-bonding network between the water molecules and charge transfer from water to the C 60 fullerene. Another one 18 suggests that the sonication process induces the covalent attachment of water hydroxyls to C 60 fullerene carbons, resulting in the formation of alcohol moieties that enable C 60 fullerene dissolution. The problem here is that the properties of C 60 FAS (including biological properties) as well as the mechanism of water solubility may depend on the method of preparation of C 60 fullerene aqueous solution. 13,16,17 Indeed, these two approaches differ by the underlying method of C 60 FAS preparation although the sonication step is presented in both methods. The question therefore arises as to whether the mechanism of solubility of C 60 fullerene in water depends on the method of C 60 FAS preparation. This question has been investigated in this article. ■ EXPERIMENTAL SECTIONSample Preparation. For the preparation of C 60 FAS, we used a saturated solution of pure C 60 fullerene (purity >99.99%) in toluene with a C 60 molecule concentration corresponding to maximum solubility near 2.9 mg/mL and the same amount of distilled water in an open beaker. The two phases that formed were treated in an ultrasonic bath. The procedure was continued until the toluene had completely evaporated and the water phase became yellow. Filtration of the aqueous solution allowed us to separate the product from un...

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[60]Fullerene is a Powerful Antioxidant in Vivo with No Acute or Subacute Toxicity

Cited by 608 publications

References 45 publications

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

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

On the Origin of C₆₀ Fullerene Solubility in Aqueous Solution

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[60]Fullerene is a Powerful Antioxidant in Vivo with No Acute or Subacute Toxicity

Cited by 608 publications

References 45 publications

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

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

On the Origin of C60 Fullerene Solubility in Aqueous Solution

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On the Origin of C₆₀ Fullerene Solubility in Aqueous Solution