Re: quinolinic acid - Possible Protective Role of Aciclovir

[Guest guest]

Here's a Pub Med reference from last month suggesting that Aciclovir

has neuroprotective properties that can limit the neurotoxicity of

QUIN. The disease context is AIDS-Related Dementia, but...

....what made this seem interesting is the method of the experiment,

which involved exposing rat brain homogenates to QUIN and Aciclovir,

but not to any viral pathogen.

So whatever they were seeing would appear to be a direct interaction

between Aciclovir, QUIN, and the brain tissues used. Note please

this is NOT a therapeutic recommendation - I am just noting a

pubished finding on a strict FWIW basis.

J Pharm Pharmacol. 2005 Jul;57(7):883-8.

" Aciclovir protects against quinolinic-acid-induced oxidative

neurotoxicity. "

Muller AC, Maharaj H, Maharaj DS, Daya S.

Division of Pharmacology, Faculty of Pharmacy, University,

Grahamstown, 6140, South Africa.

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.

PMID: 15969948 [PubMed - in process]

> > Hi,

> >

> > A 1992 paper in the journal Brain said, " We conclude that

> inflammatory

> > diseases are associated with accumulation of QUIN, kynurenic

acid

> and

> > L-kynurenine within the central nervous system, but that the

> available

> > data do not support a role for QUIN in the aetiology of

> Huntington's

> > disease or Alzheimer's disease. "

> >

> > PMID: 1422788

> >

> > ==============================

> >

> > But this week, new findings were reported in Australia. One of

the

> > authors of a paper that appeared in the journal Neuropathology

and

> > Applied Neurobiology said this week, " We found that all of the

> brains

> > of dementia patients showed quinolinic acid neurotoxicity... "

> >

> > Another said, " We found that all of the brains of dementia

> patients

> > showed quinolinic acid neurotoxicity, " said Professor Bruce

Brew,

> > Director of Neurology at St 's Hospital and Professor of

> > Medicine at the University of New South Wales (UNSW). " This acid

> kills

> > nerve cells in the brain, leading to brain dysfunction and

> ultimately

> > death. "

> >

> > " Quinolinic acid is part of a biochemical pathway called the

> kynurenine

> > pathway, " said the lead author of the research, UNSW's Dr

Gilles

> > Guillemin, who is based at the Centre for Immunology at St

> 's

> > Hospital. " The activation of that pathway is also found in other

> major

> > brain diseases including Huntington's disease, stroke, dementia

> and

> > schizophrenia. "

> >

> > http://www.rxpgnews.com/research/aging/dementia/alzheimers/

> > article_1994.shtml

> > ======================

> >

> > Thanks to Tony for pointing out the Australian findings.

> >

> > Sue ,

> > Upstate New Yorark