Doxycycline, a 2nd generation tetracycline, protects neuronal cells against glutamate- but not against 6-OHDA-induced cytotoxicity

摘要

In the present work, we showed the effects of doxycycline (Dox) on the viability of rat cortical and mesencephalic cells exposed to glutamate (Glu) and 6-OHDA, respectively, as evaluated by the MTT assay. Except at the lowest dose, Dox (0.1 to 10 ng/ml) blocked Glu cytotoxicity. At higher concentrations (0.1 to 1 |ig/ml), the effects were similar however decreasing cell viability. On mesencephalic cells, Dox (0.01 and 0.1 mug/ml) offered no protection against 6-OHDA-induced neurotoxicity. At higher doses (1 and 10 mug/ml), it decreased the cell viability, and the combination of 6-OHDA with Dox highest dose (10 mug/ml) showed an effect even greater than that seen with either 6-OHDA or Dox alone. Furthermore, Dox was very effective as an antioxidant, as demonstrated by the DPPH in vitro, and completely inhibited the myeloperoxidase (MPO) release from human neutrophils what characterizes its anti-inflammatory activity. All together, we showed that Dox is a potent antioxidant and neuroprotective agent, counteracting the Glu excitotoxicity. However, it offered no protection against the 6-OHDA-induced cytotoxicity, suggesting that the drug does not seem to directly interfere with mitochondrial dysfunctions such as those involved with the 6-OHDA action.