The prolongation of the lifespan of rats by repeated oral administration of [60] fullerene

201207 The prolongation of the lifespan

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Tarek Baati a, b, Fanchon Bourasset c, Najla Gharbi d, Leila Njim b, Manef Abderrabba e, Abdelhamid Kerkeni b, Henri Szwarc d, Fathi Moussa d, * a UMR CNRS 8612, Faculté de Pharmacie, Université Paris Sud XI, Rue J-B Clément-F92296, Châtenay-Malabry, France b Unité Elements Trace et Antioxydants, Laboratoire de Biophysique and Service d’anatomie et de Cytologie Pathologiques, CHU de Médecine de Monastir, 5000, Tunisie c Barrières Physiologiques et Réponses Thérapeutiques (EA 4123), Faculté de Pharmacie, Université Paris Sud XI, Rue J-B Clément-F92296, Châtenay-Malabry, France d Laboratoire d’Etude des Techniques et Instruments d’Analyse Moléculaire, GCAPS, EA 4041, IUT d’Orsay, Université Paris Sud XI, Plateau de Moulon, 91400 Orsay, France e Unité de Physico-Chimie Moléculaire, Ipest, Université de Carthage, 2070 Carthage, Tunisie

ABSTRACT

Countless studies showed that [60]fullerene (C60) and derivatives could have many potential biomedical applications. However, while several independent research groups showed that C60 has no acute or sub- acute toxicity in various experimental models, more than 25 years after its discovery the in vivo fate and the chronic effects of this fullerene remain unknown. If the potential of C60 and derivatives in the biomedical field have to be fulfilled these issues must be addressed. Here we show that oral adminis- tration of C60 dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) to rats not only does not entail chronic toxicity but it almost doubles their lifespan. The effects of C60-olive oil solutions in an experimental model of CCl4 intoxication in rat strongly suggest that the effect on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Pharmacokinetic studies show that dissolved C60 is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours. These results of importance in the fields of medicine and toxicology should open the way for the many possible -and waited for- biomedical applications of C60 including cancer therapy, neurodegenerative disorders, and ageing.

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