Ritonavir protects hippocampal neurons against oxidative stress-induced apoptosis.
Oxidative stress plays an important role in many neurodegenerative conditions including Alzheimer's disease and Parkinson's disease. 4-Hydroxynonenal (HNE), a lipid-soluble aldehydic product of membrane peroxidation, has been known to decrease neuronal survival by impairing Na+, K+, and -ATPase activity. HNE also increases neuronal vulnerability to excitotoxic injury and disrupts homeostasis by activating proteases which mediate the destruction of cellular protein and structure. The present study demonstrated that the hydrophobic HIV protease inhibitor, ritonavir inhibited HNE-mediated apoptosis in hippocampal primary neurons. In neurons exposed to oxidative stress induced by HNE (1 microM), ritonavir at 100 pM increased cell survival and completely abolished the apoptotic effects of HNE (P < 0.01). Ritonavir and its analogues might have useful cytoprotective effects for use in limiting the natural course of tissue injury after conditions where oxidative stress plays a role.
Wan
Wenshuai
W
Unit of Clinical and Biochemical Pharmacology, Laboratory of Clinical Studies, Division of Intramural Clinical and Biochemical Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-1256, USA.
DePetrillo
Paolo B
PB
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019438:Ritonavir / Q000494:pharmacology*
D000447:Aldehydes; D019380:Anti-HIV Agents; C027576:4-hydroxy-2-nonenal; D019438:Ritonavir