Inhibition ofEscherichia coli-Induced Meningitis by Carboxyfullerence

Abstract

The effect of a water-soluble malonic acid derivative of carboxyfullerence (C60) against Escherichia coli-induced meningitis was tested. C60 can protect the mice from E. coli-induced death in a dose-dependent manner. C60 administered intraperitoneally as late as 9 h after E. coliinjection was still protective. The C60-treated mice had less tumor necrosis factor alpha and interleukin-1β production by staining of brain tissue compared to the levels of production for nontreated mice. The E. coli-induced increases in blood-brain barrier permeability and inflammatory neutrophilic infiltration were also inhibited. These data suggest that C60 is a potentially therapeutic agent for bacterial meningitis.

Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60)

“…On the other hand, immune-mediated inflammation in response to infection can be harmful to oxidative stress-sensitive tissues such as brain. Intraperitoneal injection of carboxyfullerene completely protected mice from bacteria (E. coli)-induced lethal meningitis, while in the same conditions the classic antiinflammatory drug dexamethasone was only partly efficient [152]. Interestingly, the observed effect was not due to a direct antibacterial activity of C 60 , but resulted from fullerene-mediated The effects on ROS generation were directly assessed, except in the case of some in vivo studies, where they were indirectly inferred.…”

“…interference with the secretion of neurotoxic proinflammatory mediators TNF and IL-1 and reduction of the increase in bloodbrain barrier permeability and inflammatory neutrophilic infiltration [152]. Polyhydroxylated C 60 and N-ethyl-polyamino C 60 prevented the in vivo release of histamine and drop in body temperature in a mouse model of anaphylaxis [153].…”

Fullerenes as unique nanopharmaceuticals for disease treatment

“…Intraperitoneal injection of C 60 into naive mice induced increased expression of TNF- in brain arterioles and ependymal cells. TNF- and IL-1 production was decreased after C 60 treatment [48]. C 63 (COOH) 6 with C3 symmetry has a therapeutic effect on group A streptococcus (GAS) infection.…”

The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis

“…Drugs can be covalently attached to functional groups on the external surface of the nanotubes (Chen et al, 2001). Soluble derivatives of fullerenes have good biocompatibility and low toxicity and are under investigation as antiviral agents (Schinazi et al, 1993), antibacterial agents (Bosi et al, 2000;Tsao et al, 1999Tsao et al, , 2001, anticancer therapies (Miyata and Yamakoshi, 1997;Tabata et al, 1997a,b), antioxidants and anti-apoptosis agents for potentially treating amyotrophic lateral sclerosis and Parkinson's disease (Dugan et al, 2000). A final drug delivery approach mentioned here uses ''nanoshells'' or dielectricmetal (gold-coated silica) nanospheres.…”