Poly(ADP-ribose)polymerase is not involved in the neuroprotection exerted by azithromycin against ischemic stroke in mice.

Poly(ADP-ribose)polymerase is not involved in the neuroprotection exerted by azithromycin against ischemic stroke in mice. Eur J Pharmacol. 2016 Sep 20; Authors: Petrelli F, Muzzi M, Chiarugi A, Bagetta G, Amantea D Abstract Repurposing azithromycin has recently emerged as a promising strategy for the acute treatment of ischemic stroke. The mechanism of neuroprotection depends on the ability of this macrolide to promote polarization of microglia/macrophages towards beneficial M2 phenotypes. The immunomodulatory and anti-inflammatory effects of azithromycin, well documented in chronic inflammatory airway diseases, have been ascribed to the inhibition of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1. Since these inflammatory transcription factors are positively regulated by poly(ADP-ribose)polymerase (PARP)-1, an enzyme actively involved in ischemic brain injury, we have investigated whether the neuroprotective properties of azithromycin in ischemic stroke involve upstream modulation of PARP-1. Administration of a single dose of this macrolide antibiotic upon reperfusion reduced, to a similar extent in wild type and PARP-1 knockout mice, infarct brain damage produced by transient occlusion of the middle cerebral artery. Moreover, we demonstrated the lack of effects of azithromycin on PARP-dependent death of HeLa cells, as well as on activity of purified PARP-1 and PARP-2. Thus, azithromycin protects mic...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research