Carboxyfullerenes as neuroprotective agents

Dugan, Laura L.; Turetsky, Dorothy M.; Cheng, Du; Lobner, Doug; Wheeler, Mark E.; Almli, C. Robert; Shen, Che-Kun James; Luh, Tien‐Yau; Choi, Dennis W.; Lin, Tien‐Sung

doi:10.1073/pnas.94.17.9434

Cited by 715 publications

(471 citation statements)

References 39 publications

(40 reference statements)

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“…tection by C 3 fullerene against excitotoxic, apoptotic, and metabolic insult was observed in cortical cell cultures (97,98). A C 3 fullerene, given orally at 10 mg=kg=day, starting at 12 months of age until death reportedly extended both the life span and cognition of mice; the authors also reported the mitochondrial localization of C 3 and its ability to cross the blood-brain barrier (256,137).…”

mentioning

confidence: 88%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

465

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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confidence: 88%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

465

689

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“…Water-soluble fullerene derivatives have shown promise as drug carriers to bypass the brain and ocular barriers (Calvo et al, 1996;Da Ros and Prato, 1999;Dugan et al, 1997). They have also exhibited antitumor and antiviral activity, including inhibition of HIV protease (Bogdanovic et al, 2004;Friedman et al, 1993;Nakamura and Isobe, 2003;Schinazi et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

Roberts

Wielgus

Boyes

et al. 2008

Toxicology and Applied Pharmacology

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The water-soluble, hydroxylated fullerene [fullerol, nano-C 60 (OH) [22][23][24][25][26] ] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have assessed fullerol's potential ocular toxicity by measuring its cytotoxicity and phototoxicity induced by UVA and visible light in vitro with human lens epithelial cells (HLE B-3). Accumulation of nano-C 60 (OH) [22][23][24][25][26] in the cells was confirmed spectrophotometrically at 405 nm and cell viability estimated using MTS and LDH assays. Fullerol was cytotoxic to HLE B-3 cells maintained in the dark at concentrations higher than 20 µM. Exposure to either UVA or visible light in the presence of >5 µM fullerol induced phototoxic damage. When cells were pretreated with non-toxic antioxidants: 20 µM lutein, 1 mM N-acetyl cysteine, or 1 mM L-ascorbic acid prior to irradiation, only the singlet oxygen quencher lutein significantly protected against fullerol photodamage. Apoptosis was observed in lens cells treated with fullerol whether or not the cells were irradiated, in the order UVA > visible light > dark. Dynamic light scattering (DLS) showed that in the presence of the endogenous lens protein α-crystallin, large aggregates of fullerol were reduced. In conclusion, fullerol is both cytotoxic and phototoxic to human lens epithelial cells. Although the acute toxicity of water soluble nano-C 60 (OH) 22-26 is low, these compounds are retained in the body for long periods, raising concern for their chronic toxic effect. Before fullerols are used to deliver drugs to the eye, they should be tested for photo-and cytotoxicity in vivo.

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“…We used three different free radicals scavengers to assess the role of ROS in cisplatin-induced apoptosis. C 60 (D3) is an effective scavenger of hydroxyl and superoxide radicals (Dugan et al, 1997;Hsu et al, 1998), MnTBAP is a superoxide dismutase mimic, and N-acetylcysteine (NAC) detoxifies free radicals to prevent DNA damage (Malins et al, 2002). C 60 (D3) effectively suppressed apoptosis induced by g-irradiation and cisplatin (Figure 7b).…”

Section: Ros Are Required For Cisplatin-induced Apoptosismentioning

confidence: 99%

“…FITCconjugated anti-Fas antibody, human Fas-Fc, His-tagged FasL, and anti-His antibody were purchased from R&D (Minneapolis, MN, USA). The regioisomer with D3 symmetry of water-soluble carboxylic acid C 60 derivatives (carboxylfullerenes) was synthesized as previously described (Dugan et al, 1997). Dichlorodihydrofluorescein diacetate (DCFCA) and dihydroethidium (DHE) were obtained from Molecular Probes (Eugene, OR, USA).…”

Section: Reagentsmentioning

confidence: 99%

DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation

et al. 2003

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DNA-damaging reagents may kill tumor cells through the generation of reactive oxygen species (ROS). Cytotoxic reagents may also induce apoptosis of cancer cells in Fas-FADD-dependent manners. In this study, we explored the possible link between these two apparently distinct pathways in T leukemia cell Jurkat. Our results demonstrated that c-irradiation, similar to cisplatin, induced apoptosis by triggering Fas aggregation and activating FADDcaspase-8 apoptotic cascade. The absence of caspase-8 or Fas greatly reduced the sensitivity to apoptosis mediated by DNA-damaging agents. In addition, apoptosis induced by cisplatin and c-irradiation, but not by Fas, was inhibited by ROS scavengers, including N-acetyl cysteine, MnTBAP, and C 60 . Importantly, these ROS scavengers effectively prevented the clustering of Fas receptor induced by cisplatin and c-irradiation. Our results suggest that cisplatin and c-irradiation promote ROS production, which in turn contributes to Fas receptor aggregation and cell death. The novel coupling between ROS and Fas clustering likely plays a significant role in apoptosis triggered by DNA-damaging reagents in Fas-expressing leukemia cells.

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Carboxyfullerenes as neuroprotective agents

Cited by 715 publications

References 39 publications

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation

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