Protective role of carnosine after INOS induction by LPS and INF-gamma treatment in primary rat astroglial cellcultures

Carnosine, a b-alanyl-histidine dipeptide, is present in quite high concentration in brain, it seems to exert a protective effect against cell damage caused by oxidants. In the present study we investigated the effect of carnosine addition (20 mM) against NO-induced oxidative stress in rat astroglial cell cultures. We measured cell viability (MTT), nitrite production, LDH release into culture medium and the effect of a specific inhibitor of iNOS, the N-mono-metil-arginine (NMMA 1 mM). After LPS (4 lg/ml) and INF-c (400U/ml) treatment, a decrease of cell viability and an increase of LDH and nitrite release was observed. Interestingly all these effects were prevented by carnosine addition. Moreover, as determined by ESI Mass spectra, carnosine was able to trap NO forming NO-carnosine adducts. Furthermore an increase of cell survival and a decrease of LDH and nitrite release were also observed after NMMA addition demonstrating that oxidative stress in these conditions is due to iNOS induction. The effects of carnosine treatment in all the experimental conditions tested, demonstrate a marked protection of this compound against NO-induced oxidative stress. The data obtained strongly suggest an antioxidant action of carnosine, however further investigations are necessary to better clarify its role for possible clinical application.