Carboxyfullerene Prevents Iron‐Induced Oxidative Stress in Rat Brain

Abstract

Carboxyfullerene, a water-soluble carboxylic acid derivative of a fullerene, was investigated as a protective agent against iron-induced oxidative stress in the nigrostriatal dopaminergic system of anesthetized rats. Intranigral infusion of exclusive carboxyfullerene did not increase lipid peroxidation in substantia nigra or deplete dopamine content in striatum. Infusion of ferrous citrate (iron II) induced degeneration of the nigrostriatal dopaminergic system. An increase in lipid peroxidation in substantia nigra as well as decreases in K ϩ -evoked dopamine overflow and dopamine content in striatum were observed 7 days after the infusion. Co-infusion of carboxyfullerene prevented iron-induced oxidative injury. Furthermore, tyrosine hydroxylase-immunoreactive staining showed that carboxyfullerene inhibited the iron-induced loss of the dopaminergic nerve terminals in striatum. The antioxidative action of carboxyfullerene was verified by in vitro studies. Incubation of brain homogenates increased the formation of the Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Both autooxidation (without exogenous iron) and iron-induced elevation of lipid peroxidation of brain homogenates were suppressed by carboxyfullerene in a dose-dependent manner. Our results suggest that intranigral infusion of carboxyfullerene appears to be nontoxic to the nigrostriatal dopaminergic system. Furthermore, the potent antioxidative action of carboxyfullerene protects the nigrostriatal dopaminergic system from iron-induced oxidative injury. Key Words: Carboxyfullerene -Iron-Oxidative injury-K ϩ -evoked dopamine overflow-Lipid peroxidation.

X-ray crystal structure of an anti-Buckminsterfullerene antibody Fab fragment: Biomolecular recognition of C 60

“…In 1985, a third allotrope was discovered and dubbed Buckminsterfullerene because of its geodesic character (1). The preparation of fullerenes in workable quantities led first to applications in chemical and engineering processes and subsequently to the suggested use of fullerenes in biological applications (2)(3)(4) and as templates for the design of experimental pharmaceutical agents, including those with anti-viral (5-9), antioxidant (8)(9)(10)(11)(12), chemotactic (13), and neuroprotective (14) activities.…”

C60-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

“…The FAB-MS analysis of compound 3 gives the molecular ion peak at m/z 1361 (M+H) + and a relevant fragment at m/z 720 (M+H-ebselen malonate) + . The UVVis spectrum of compound 3 contains a typical medium intensity absorption band at around 430 nm, which is characteristic of most dihydrofullerenes 23 and further proves that compound 3 is a [6,6]-closed methanofullerene.…”

“…For example, carboxyfullerenes prevent apoptotic injury of cultured cortical neurons evoked by N-methyl-D-aspartate and β-amyloid peptide, 5 and inhibit iron-induced oxidative stress in rat brain. 6 The same carboxyfullerenes were also reportedly able to inhibit cerebellar granule cell apoptosis, possibly by reducing the generation of ROS. 7 Other fullerene derivatives, such as fullerenol, hexasulfobutylated C 60 (FC4S) and C 60 (glucosamine) 6 , also showed neuroprotective activity related to their antioxidative property.…”

“…6 The same carboxyfullerenes were also reportedly able to inhibit cerebellar granule cell apoptosis, possibly by reducing the generation of ROS. 7 Other fullerene derivatives, such as fullerenol, hexasulfobutylated C 60 (FC4S) and C 60 (glucosamine) 6 , also showed neuroprotective activity related to their antioxidative property. Fullerenol demonstrated to be a powerful scavenger for the free radicals induced by I/R (ischemia/reperfusion) injury of the small intestine.…”

“…8 Hexasulfobutylated C 60 (FC4S) can be employed as a free radical remover in the biological system. 9 Recently, C 60 (glucosamine) 6 has been found to prevent renal I/Rinduced apoptosis formation and superoxide generation. 10 All these results reveal that fullerene and its derivatives possess antioxidative activity and may be useful as neuroprotective agents in several acute or chronic neurodegenerative diseases.…”