Nicotine protects rat brain mitochondria against experimental injuries.
Epidemiological studies have reported that cigarette smoking may protect from neurodegenerative diseases such as Parkinson's disease. These protective effects are thought to be mediated by nicotine. Recent data showed that nicotine significantly decreases respiratory control ratio (RCR) and superoxide anion generation of brain mitochondria. Thus, we investigated nicotine effects on rat brain in two experimental models: first, an in vitro anoxia/reoxygenation experiment and secondly, an in vivo rotenone-induced Parkinson-like syndrome. Anoxia/reoxygenation impaired mitochondrial respiration by 43.68% whereas in the presence of nicotine, it was less impaired, by 31.1% at 10(-7) M. In rats chronically administered rotenone (3 mg/kg/day), we observed profound mitochondrial damage: the RCR decreased by 50.36% and the superoxide anion generation and the membrane anisotropy increased by 56.03 and 13.43%, respectively. All of these indications of mitochondrial damage were limited by chronic administration of nicotine. Nicotine developed mitochondrial effects in vivo and in vitro at very low concentration. All these results were in accordance with epidemiological studies, which report a protective effect of nicotine in neurodegenerative diseases. Thus, we propose that one effect of nicotine is to preserve mitochondrial functions of the rat central nervous system.
Cormier
A
A
Laboratoire de Pharmacologie, Department de Pharmacologie, Faculté de Médecine de Paris XII, 8 rue de General Sarrail, F94010 Creteil, France. a.cormier@univ-paris12.fr
Morin
C
C
Zini
R
R
Tillement
J-P
JP
Lagrue
G
G
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D009538:Nicotine