The prolongation of the lifespan of rats by repeated oral administration of [60] Fullerene 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
(Excerpted from the journal Biomaterials, March 10, 2012.)
A b s t r a c t 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 subacute 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 administration 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.
Conclusion The effect of pristine C60 on lifespan emphasizes the absence of chronic toxicity. These results obtained with a small sample of animals with an exploratory protocol ask for a more extensive studies to optimize the intestinal absorption of C60 as well as the different parameters of the administration protocol: dose, posology, and treatment duration. In the present case, the treatment was stopped when a control rat died at M17, which proves that the effects of the C60 treatment are long-lasting as the estimated median lifespan for C60-treated rats is 42 months. It can be thought that a longer treatment could have generated even longer lifespans. Anyway, this work should open the road towards the development of the considerable potential of C60 in the biomedical field, including cancer therapy, neurodegenerative disorders and ageing. Furthermore, in the field of ageing, as C60 can be administered orally and as it is now produced in tons, it is no longer necessary to resort to its water-soluble derivatives, which are difficult to purify and in contrast to pristine C60 may be toxic.