Rifampicin inhibits neurodegeneration in the optic nerve transection model in vivo and after 1-methyl-4-phenylpyridinium intoxication in vitro.
Rifampicin is an antibacterial drug which is highly effective in the treatment of tuberculosis and leprosy. It has been shown to exert antioxidative as well as anti-apoptotic effects. In this study, the neuroprotective effect of rifampicin was examined after 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic cell death in vitro, and on the survival of retinal ganglion cells after optic nerve transection in vivo. Rifampicin administration significantly increased the number of surviving dopaminergic neurons after MPP+ intoxication as compared to control cultures. No cytotoxic effects were noted even at final rifampicin concentrations of 100 microM. In the rifampicin-treated group, retinal ganglion cell survival was significantly increased after axotomy as compared with vehicle-treated and phosphate-buffered saline-treated control animals. These results suggest that rifampicin is able to prevent neuronal degeneration in cell death paradigms involving oxidative stress and activation of apoptotic pathways. It may thus play a role in the future treatments of neurodegenerative disorders.
Kilic
Ulkan
U
Department of Neurology, University Hospital Zürich, Frauenklinikstr. 26, 8091, Switzerland. uelkan.kilic@usz.ch
Kilic
Ertugrul
E
Lingor
Paul
P
Yulug
Burak
B
Bähr
Mathias
M
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000209:etiology; D009474:Neurons / Q000187:drug effects*; D020221:Optic Nerve Injuries / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects; D012293:Rifampin / Q000627:therapeutic use*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004791:Enzyme Inhibitors; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D012293:Rifampin