Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C60

Ueng, Tzuu‐Huei

doi:10.1016/s0378-4274(97)00071-4

Cited by 118 publications

(48 citation statements)

References 26 publications

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“…The highest dosage used in this study (a total of 80 mg/kg by air pouch and intraperitoneal injection) was far below the toxic dose. The LD 50 of fullerenol in mice by intraperitoneal injection is 1,000 mg/kg (19). For therapeutic purposes, the dosage can be increased further in future studies.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Group A Streptococcus Infection by Carboxyfullerene

Tsao

Luh

Chou

et al. 2001

Antimicrob Agents Chemother

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The effect of a water-soluble trimalonic acid derivative of fullerene, carboxyfullerene, against Streptococcus pyogenes infection was tested. Pretreatment with carboxyfullerene was able to protect mice from S. pyogenes infection in an air pouch model. S. pyogenes-induced death and skin injury were inhibited dose dependently by carboxyfullerene. Administration of carboxyfullerene via the peritoneum and air pouch at 3 h post-S. pyogenes infection was able to protect 33% of mice from death. Surveys of exudates of the air pouch of carboxyfullerenetreated mice revealed that survival of infiltrating neutrophils was prolonged and that the bacteria were eliminated as a result of enhanced bactericidal activity of the neutrophils. Furthermore, carboxyfullerene was able to directly inhibit in vitro growth of S. pyogenes. These data suggest that carboxyfullerene can be considered an antimicrobial agent for group A streptococcus infection.The incidence of infection with the group A streptococcus (GAS) Streptococcus pyogenes has increased worldwide and is still associated with a high mortality rate, especially when GAS infection induces necrotizing fasciitis and streptococcal toxic shock syndrome (1,3,11,14,15,21). Certain virulence factors involved in the pathogenesis of GAS infection have been reported. These include cell surface molecules such as M protein, opacity factor, the hyaluronic acid capsule, C5a peptidase, and the streptococcal inhibitor of complement, as well as secreted products such as pyogenic exotoxins, cysteine proteinase, streptolysins O and S, hyaluronidase, streptokinase, and other enzymes (3,12,15). Empirical therapy for GAS infection includes antibiotics, aggressive surgery, and intravenous administration of immunoglobulin (21,22).Buckminsterfullerenes (fullerene [C 60 ]) have attracted much attention since their discovery and large-scale synthesis. Fullerene is characterized as a "radical sponge" because of its unique cage structure, which allows it to interact effectively with free radicals (7). However, native C 60 is soluble only in organic solvents and so cannot be applied to medical therapy. A water-soluble trimalonic acid derivative of fullerene (carboxyfullerene [C 63 (COOH) 6 ]) has been synthesized and has been found to be an effective neuroprotective antioxidant both in vitro and in vivo (2, 9). Carboxyfullerene is a powerful free radical scavenger and can protect cells from apoptosis in various systems (4, 5). In previous studies, we found that carboxyfullerene was able to inhibit the development of Escherichia coli-induced meningitis (18) by modulating the activity of neutrophils (16). In the present study, the effect of carboxyfullerene on gram-positive bacterial infections was evaluated. Using an air pouch GAS infection model, which mimics localized fasciitis (8), we found that carboxyfullerene was able to inhibit GAS infection by both modulating the bactericidal activity of infiltrating neutrophils and directly inhibiting the growth of S. pyogenes. MATERIALS AND METHODSMice. C57BL/6 (B6...

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Section: Discussionmentioning

confidence: 99%

Inhibition of Group A Streptococcus Infection by Carboxyfullerene

Tsao

Luh

Chou

et al. 2001

Antimicrob Agents Chemother

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“…11,12 Alternatively, nanomaterials may impede autophagy by inhibiting lysosomal enzymes 13 or disrupting cytoskeleton-mediated vesicle trafficking, 14 resulting in diminished autophagosome-lysosome fusion. Nanoparticles certainly share properties with substances known to cause lysosomal disorders, 15 including lysosomal localization, 16,17 enzyme inhibiting ability, 18,19 and biopersistence. For example, a water-soluble fullerene derivative causes lysosome-overload nephrosis in rats, which is typically the result of inhibition of lysosomal protein degradation.…”

Section: Hypothesis: Nanoparticle-autophagy Interaction In Neurodegermentioning

confidence: 99%

Role for nanomaterial-autophagy interaction in neurodegenerative disease

Stern

Johnson²

2008

Autophagy

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Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nanotechnology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated elevated levels of autophagic vacuoles upon exposure of cells to certain nanomaterials, including carbon-and metal-based nanoparticles. While this apparent increase in autophagic activity may be an appropriate cellular response toward nanomaterial clearance, often the interaction between nanomaterials and the autophagy pathway is disruptive, resulting in severe morphological changes and coincident cell death. Interestingly, epidemiological studies have identified an association between exposure to combustion-derived ambient particles (which are predominantly nanoscale) and neurological conditions with Alzheimer's and Parkinson's disease-like pathologies. Becuse impaired autophagy may play an important role in the pathogenesis of these and other diseases, it is intriguing to speculate about the plausible involvement of nanoscale particulates in this process. The interaction of nanomaterials with the autophagy pathway, and the potential negative consequences of resulting autophagy dysfunction, should be explored further.

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“…In the groups 0.1-1 g/kg, a minor decrease was observed in body weight within 2-3 days after the administration, but all surviving animals had normal body weight 2 weeks after the administration. Liver cytochrome P450 isoenzymes, NADPH-cytochrome P450 reductase and cytochrome b 5 were unaffected at 100 mg/kg but reduced at ≥0.5 g/kg [71].…”

Section: In Vivo Toxicitymentioning

confidence: 90%

In vivo Biology and Toxicology of Fullerenes and Their Derivatives

Nielsen

Roursgaard

Jensen

et al. 2008

Basic Clin Pharma Tox

165

116

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Fullerenes represent a group of nanoparticles discovered in 1985. They are spherical molecules consisting entirely of carbon atoms (C x ) to which side chains can be added, furnishing compounds with widely different properties. Fullerenes interact with biological systems, for example, by enzyme inhibition, causing phototoxic reactions, being scavengers of reactive oxygen species and free radicals, in addition to being able to initiate free radical reactions. Absorption, distribution and excretion strongly depend on the properties of the side chains. The pristine C 60 has a very long biological half-life, whereas the most water-soluble derivatives are eliminated from the exposed animals within weeks. A long biological half-life raises concern about bioaccumulation and long-term effects. In general, the acute oral, dermal and airway toxicity is low. However, few relevant experimental studies of repeated dose toxicity, reproductive toxicity and carcinogenic effect are available. The data suggest that direct DNA damaging effects are low, but formation of reactive oxygen species may cause inflammation and genetic damage. Apparently, it is dose-dependent whether a beneficial or an adverse effect occurs.Nanoparticle-based technology is a rapidly growing area of interest [1,2], which takes advantage of the fact that the specific surface area increases dramatically at small-size particles, thus these particles may have properties that are different from corresponding particles with larger size [1][2][3]. This also applies for toxicity, which, among other factors, depends on surface area, chemical composition and shape [3]. Nanoparticles (<100 nm, at least in one dimension) comprise naturally occurring (e.g. combustion products) and engineered/ manufactured nanoparticles [3]. Nanoparticles are used, for example, in electronic equipments [1,2] In a recent publication from the German chemical industry, it appeared that the most commonly used manufactured nanoparticles are sialic acid, metal nanoparticles, metal oxides, silicate, carbon black, nanosilver, pharmaceutical products and other nanoparticles [7]. The similar bulk materials were used in the UK in addition to niche products such as fullerenes, carbon nanotubes, nanowires, quantum dots and other nanoparticles [2]. A large-scale production plant for fullerene has recently been opened in Japan, allowing a production of a high tonnage per year [2]. Due to the high electron affinity and superior ability to transport charge, fullerene-based solar cells are currently accepted as being the most effective for this purpose [8]. The in vivo biology and toxicology of fullerenes are the subjects of this MiniReview not only as fullerenes are interesting due to their technical properties, but also as they are considered candidates for new drugs, new antioxidants and new radicalscavenging compounds [5,9,10]. Further examples of in vitro effects are available from the recent review [10]. In vitro toxicity is only considered where assumed to contribute to the understanding ...

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Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C60

Cited by 118 publications

References 26 publications

Inhibition of Group A Streptococcus Infection by Carboxyfullerene

Inhibition of Group A Streptococcus Infection by Carboxyfullerene

Role for nanomaterial-autophagy interaction in neurodegenerative disease

In vivo Biology and Toxicology of Fullerenes and Their Derivatives

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