X-Message-Number: 12420
Date: Tue, 14 Sep 1999 16:28:00 -0400
From: Jan Coetzee <>
Subject: NOS and ROS

Dual action drug protects brain against stroke,
trauma

NEW YORK, Sep 13 (Reuters Health) -- A new drug with two different
injury
protection properties reduces brain cell damage in animal models of
stroke and
head trauma.

Two key processes contribute to the damage seen after ischemia -- an
interruption of blood flow
to the brain. An enzyme called nitric oxide synthase (NOS) causes
overproduction of a damaging
chemical, nitric oxide (NO). At the same time, strong oxygen compounds
called reactive oxygen
species (ROS) cause widespread cell damage.

``Our results suggested that controlling both ROS and NO is more
efficient (in preventing brain
damage) than the inhibition of only one of these,'' according to
Pierre-Etienne Chabrier from
Beaufour-Ipsen Research Laboratories in Cedex, France, and colleagues.
Their results are
published in the September issue of the Proceedings of the National
Academy of Sciences.

The researchers tested BN 80933 in rats and gerbils with stroke-like
conditions and in mice
subjected to head trauma. BN 80933 contains an antioxidant (a chemical
that prevents ROS
effects) linked to an NOS blocker. The drug proved effective in
preventing cell death, the report
indicates.

BN 80933 reduced the death of brain cells by 60% to 70% in rats, and the
rats that received BN
80933 had better functioning after their ischemic episodes, the
scientists explain.

In gerbils subjected to ischemia of the entire brain, BN 80933 more than
doubled the number of
surviving brain cells, the investigators report.

Mice that sustained head trauma were also protected by BN 80933,
according to the results.
When administered 5 minutes after injury, BN 80933 reduced the damage to
the mice by 48% to
58%, depending upon the dose given.

``All these results indicate that BN 80933 represents a class of
potentially useful therapeutic
agents for the treatment of stroke or trauma and possibly
neurodegenerative disorders that
involve both NO and ROS,'' Chabrier and colleagues conclude.

``Most important is that the protection conferred by this agent is
sustained; thus, it can be given 4
to 8 hours after injury and still provide significant neuroprotection,''
writes Valina Dawson of
Johns Hopkins University School of Medicine in Baltimore, Maryland, in a
related commentary.
``This approach, which one could envisage being employed with
alternative targets, is
particularly innovative.''

SOURCE: Proceedings of the National Academy of Sciences USA
1999;96:10824-10829,
10557-10558.

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