Aciclovir protects against quinolinic-acid-induced oxidative neurotoxicity.
AIDS-related encephalopathy, including AIDS dementia complex (ADC) and the opportunistic disease, herpes simplex encephalitis (HSE), are postulated to arise due to the release of neurotoxic products, such as quinolinic acid (QUIN), by activated microglial cells in the brain. QUIN causes a cascade of events to occur, which leads to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. The antiherpes antiviral aciclovir has been reported to protect against neuron loss in HSE, but the mechanism for this neuroprotection is unknown. Therefore, this study was conducted to investigate whether aciclovir has the ability to inhibit QUIN-induced lipid peroxidation in rat brain homogenates, after in-vitro and in-vivo exposure to QUIN and aciclovir. The thiobarbituric acid (TBA) assay was the method used to analyse lipid peroxidation. Rat brains were also examined histologically after in-vivo exposure to visually assess whether neuron loss was suppressed. The results show that aciclovir inhibits the QUIN-induced lipid peroxidation, in a dose-dependent manner. Furthermore, aciclovir reduced necrosis of hippocampal neurons and retained the characteristic morphology, integrity and arrangement of these cells. Thus, it appears that aciclovir has neuroprotective properties, which could possibly be useful in the treatment of AIDS-related encephalopathy.
Müller
A C
AC
Division of Pharmacology, Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa.
Maharaj
H
H
Maharaj
D S
DS
Daya
S
S
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000503:physiopathology*; D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001921:Brain; D006624:Hippocampus / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents; D018384:Oxidative Stress; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species
D000998:Antiviral Agents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017378:Quinolinic Acid; D000212:Acyclovir