Protective effects of fusidic acid against sodium nitroprusside-induced apoptosis in C6 glial cells.

Abstract

Fusidic acid, a steroidal antibiotic, possesses antimicrobial, antioxidant, and anti-inflammatory properties, but the effect of fusidic acid against neurodegenerative disease-related cell death has not been studied. Here, we investigated the protective effects of fusidic acid on sodium nitroprusside (SNP)-induced toxicity in C6 glial cells. Fusidic acid (5-20 μM) prevented SNP (100 μM)-induced cell death dose dependently, and effectively attenuated SNP-induced generation of nitric oxide (NO), total reactive oxygen species (ROS), and peroxynitrite (ONOO). Fusidic acid (20 μM) pretreatment significantly suppressed SNP (100 μM)-induced apoptotic events, such as nuclear condensation and caspase-3 activation. In addition, fusidic acid effectively attenuated SNP-induced endoplasmic reticulum (ER) stress markers, such as GRP78, IRE1, ATF6, PERK, XBP1s, eIF2α, CHOP, and caspase-12. A specific adenosine monophosphate-activated protein kinase (AMPK) inhibitor, compound C (10 μM), reversed the preventive effects of fusidic acid against SNP-induced cytotoxicity, CHOP elevation, and caspase-3 activation. These results suggest that fusidic acid can protect C6 glial cells against cytotoxicity, through the regulation of AMPK pathway and apoptotic events.