Scavenging effects of terbinafine on free radicals in vitro

One of the goals of antifungal therapy is to combine an anti-inflammatory a ctivity with antimycotic properties, and therefore it is interesting to eva luate the capacity of active antifungal drugs to interfere with different p hases of the inflammatory reaction. In order to identify a possible scaveng er property of free radical species of the antifungal agent terbinafine, we studied its activity on the reduction of nitrotetrazolium blue chloride (N TB), induced by superoxide anions with the ultraviolet (UV)- and chemical-i nduced peroxidation of unsaturated lipid targets. NTB reduction was followe d by spectrophotometer and the decomposition of squalene or methyl arachido nate by gas chromatography-mass spectrometry. Terbinafine (20 mu g and over ) was capable of significantly inhibiting NTB reduction, indicating that th e drug scavenges superoxide anion radicals. In these conditions no modifica tions of the concentration of the drug, as evaluated by high performance li quid chromatography, were observed. The UV- or chemically induced peroxidat ion of squalene and arachidonic acid was significantly reduced in the prese nce of 50 mu g of terbinafine, suggesting that the substance interferes wit h the chemical properties of peroxyl radicals. In all the tests used the de gree of inhibition was proportional to the amount of free radicals generate d, In conclusion our results indicate that terbinafine, at therapeutic conc entrations, can be considered to be a free radical interceptor in vitro and could exert a mild anti-inflammatory activity in vivo.