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x011 at Lehigh.EDU x011 at Lehigh.EDU
Wed Feb 8 08:30:32 EST 1995

I thought that to much sleep therefore to much melatonin lowered your life
span.  Ron Blue
In article <RMCOHEN.5.000C3B63 at AHS.watstar.uwaterloo.ca>, RMCOHEN at AHS.watstar.uw
aterloo.ca writes:
>       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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