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RMCOHEN at AHS.watstar.uwaterloo.ca RMCOHEN at AHS.watstar.uwaterloo.ca
Tue Feb 7 12:13:55 EST 1995

	I was wondering if anyone would care to comment on the following 
citation and abstract that I pulled off Medline.  Is there any reason to 
doubt the voracity of its claims?  The same researchers have published an 
article in the New York Academy of Sciences, proposing that melatonin has 
anti-aging properties, possibly due in part to its antioxidant ability.  
Also, at what amounts does melatonin elicit a toxic response in humans, and 
what are some of the metabolic, hormonal, or homeostatic disruptions that 
can occur with prolonged melatonin comsumption in humans?  Recent journal 
references would be of great help.		
	I am aware that melatonin is being studied intensely in conjuction 
with IL-2 in the prevention of certain cancers.  From what I have read, it 
seems to lower the toxicity associated with IL-2 administration; while 
concurrently proving to be a statistically significant chemotherapeutic  
modality in the treatment of cancer.

<TITLE>MEDLINE Database, 1987 to date Document Reader</TITLE>
Interactions of the pineal hormone melatonin with oxygen-centered free
radicals: a brief review.
Reiter RJ
Department of Cellular and Structural Biology, University of Texas
Health Science Center, San Antonio 78284-7762.
<i>Braz J Med Biol Res 26: 1141-55 (1993)</I>
Melatonin,N-acetyl-5-methoxytryptamine, is a hormonal product of the
pineal gland. Its synthesis is higher at night than during the day in
all vertebrates including man. Once melatonin is produced in the pineal
gland it is quickly released into the vascular system. The rapid release
of melatonin is generally believed to relate to its high lipophilicity
which allows it to readily pass through the membrane of the pinealocytes
and the endothelial cells which line the capillaries. The result of the
nocturnal synthesis and secretion of melatonin is high blood levels at
night. Also because of its highly lipophilic nature, melatonin from the
blood readily escapes into every other bodily fluid and all cells in the
body. Until recently it was generally thought that melatonin's action
in the organism depended on its exclusive interaction with specific
receptors on cells located in discrete locations. Certainly, the
interactions of melatonin with these membrane-bound receptors are
believed to mediate the endocrine and circadian rhythm effects of
melatonin. It was recently discovered, however, that melatonin's primary
action may not depend on the previously described membrane receptors.
We have found that melatonin is a very potent hydroxyl radical
scavenger; free radicals and the hydroxyl radical in particular, because
of its very high reactivity, can be extremely damaging to
macromolecules in cells. Compared to glutathione and mannitol, two well
known free radical scavengers, melatonin is a more powerful scavenger
and affords protection of molecules, especially DNA, from oxidative
damage. Melatonin's extremely high diffusibility is important for its
scavenging action because this feature allows it to enter all cells and
every subcellular compartment. Whereas the free radical quenching
activity of melatonin does not require a receptor, we also have evidence
that it may be bound in the nucleus thereby providing on-site
protection to DNA. Besides scavenging the highly toxic hydroxyl radical,
melatonin also stimulates glutathione peroxidase activity which
metabolizes the precursor of the hydroxyl radical, hydrogen peroxide, to
water. Thus, melatonin has at least two means to protect the cell from
oxidative damage, i.e., it breaks down hydrogen peroxide to harmless
water and, in the event any hydroxyl radicals are formed, melatonin
scavenges them. Melatonin may be the premier molecule to protect the
organism from oxidative damage.
<P><B>Mesh Headings</B><DL>
<DD>Age Factors<BR>
<DD>Circadian Rhythm<BR>
<DD>DNA Damage<BR>
<DD>Free Radical Scavengers<BR>
<DD>Free Radicals<BR>
<DD>Glutathione Peroxidase*<BR>
<DD>Hydroxyl Radical*<BR>
<DD>Support, U.S. Gov't, Non-P.H.S.<BR>
</DL><P><B>Unique Identifier: </B>
<P><B>Chemical Identifiers (Names)</B><DL>
<DD>EC (Glutathione Peroxidase)<BR>
<DD>(Free Radical Scavengers)<BR>
<DD>(Free Radicals)<BR>
<DD>3352-57-6 (Hydroxyl Radical)<BR>
<DD>73-31-4 (Melatonin)<BR>

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