Jo Robinson jor at teleport.com
Tue Nov 21 19:04:15 EST 1995

DocCLIPPER (docclipper at aol.com) wrote:
: How was it determined that melatonin was indeed an antioxidant?  Was this
: a seredipitous event or were there clues to this unexpected property.
: And then how can you determine exactly where in the cellular metabolism,
: the melatonin exhibits antioxidant properties?  
:                                          Peter

As in many scientific discoveries, the realization that melatonin was
a potent antioxidant happened as a result of trying to solve a puzzle.
In this case, Russ Reiter and his crew at UTHSC were trying to understand
why melatonin was affecting a particular enzyme inside heart cells,even
though there were no receptors on those cells. {The enzyme is the
[CA2+ Mg2+]-dependent ATPase enzyme.)  It's an inviolable rule
of hormones: no receptors; no reaction.  And yet this enzyme was clearly
being affected by melatonin. 

Then it was learned that this enzyme is influenced by the redox state of
the cell.  Could it be that melatonin was scavenging free radicals inside
the cell, influencing the enzyme indirectly?  Reiter et al conducted an
in vitro experiment and discovered that melatonin had very potent
antioxidant properties.  [See "Melatonin: a potent, endogenous hydroxyl
radical scavenger" Endocrine Journal 1993; 1:57-60.]

THe way that you determine which part of the cell is being protected
from free radical damage is by exposing organisms to free radical -generating
compounds known to target  specific parts of the cell. For example, 
in one such experiment, rats were exposed to paraquat, a pesticide
 known to target cell membranes.  Animals pre-exposed to melatonin
 had virtually no lipid peroxidation of the membranes -- in fact, melatonin
provided a greater level of protection than  has been seen by any other
 antioxidant. ["Potent protective effect of melatonin on in vivo
 paraquat-induced oxidative damage in rats." [ Life Sciences 1993;
	 Later experiments exposed rats to toxins known to cause extensive
 DNA damage -- safrole, for example.  Once again, melatonin afforded near
 total protection to the DNA molecule, even though the rodents were
 exposed to 750 times more safrole than melatoin.
 (The amount of damage is determined by laboriously counting DNA "adducts.
	  [See Cancer Letters 1993;70:65-71.)
	Melatonin has also been shown to protect proteins within the cell,
a fact that was demonstrated by its ability to prevent cataracts in rats.
(THe lens of the eye is approximately 98% protein.)
	Step by step, Reiter, and now others around the world, are
demonstrating melatonin's phenomenal, unprecedented ability to protect
every cell in the body -- and every compartment in every cell -- from
free radical damage.
	For a general review of melatonin's antioxidant properties, I
recommend "A review of the evidence supporting melatonin's role as an
antioxidant." J. or Pineal Research 1995; 18:1-11.  For a more readable,
engaging account, I humbly suggest our jointly authored book, which
concludes with 40 pages of line-specific scientific references. r

Coauthor, Melatonin: Your Body's Natural WOnder Drug  (Bantam 1995)

For a melatonin FAQ, go to http://www.teleport.com/~jor
)    --
|       Jo Robinson		    |            jor at teleport.com             |
|      (503)284-4676                |     2826 NE 18th Portland, OR 97212     | 

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