MadSci Network: Biochemistry

Re: Is free radical scavenging an anti-inflammatory mechanism?

Date: Mon Feb 14 20:05:09 2000
Posted By: Mark Sullivan, Medical Student
Area of science: Biochemistry
ID: 947980584.Bc

Free radicals are highly reactive compounds generated through various 
chemical reactions which cause damage to cells.  Most free radicals are 
oxygen derived byproducts of normal cell functions like aerobic 
respiration(like Hydrogen peroxide, and superoxide anion).  Free radicals 
are chemical species that have a single unpaired electron in the outer 
shell.  The way they react is that these free radicals are attracted to 
things in the cell like lipids, which compose the outer surface of the cell 
memebrane and other organelles, and of course DNA.  
     What happens when they damage lipids and DNA?  First is that free 
radicals can be auto catalytic.  When the OH- free radical attacks lipids, 
it converts the lipid into a lipid peroxide which is in itself a free 
radical that can go on to damage other lipids.  Lipids make up the cell's 
membrane which functions to control the cell's internal versus external 
chemical environment.  If the damage to this membrane is extensive enough, 
the cell cannot regulate the concentration of ions inside the cell, leading 
to cell death.  Protiens can be damaged as well, leading to loss of 
enzymatic function and cell death.  DNA strands are broken, which can cause 
problems in replication or transcribing DNA, leading to cell death or even 
uncontrolled cell growth.  Other compounds can become free radicals when 
they are modified by normal detoxifying proteins called P-450 proteins.  A 
good example is Carbon tetracholride(CCl4).  P-450 in the liver especially 
modifies this compund to CCl3-, which can then generate lipid peroxides and 
initiate the free radical autocatalytic cascade.  In this case there is 
extensive liver damage.
    Inflammation occurs when there is extensive cell death whether it be 
from free radical damage alone or tissue trauma etc.  The body is sending 
neutrophils in to clean up the mess.  Neutrophils not only engulf cellular 
debris and kill dying cells by the use of free radicals, but they are also 
attracted to the site of injury by free radicals.  Macrophages are 
stimulated to take up oxidized compounds via their "scavenger receptors", 
and this is especially seen when taking up oxidized cholesterol.  Free 
radical scavenging compunds like Vit E, and Vit C work by reducing the 
action of free radicals and thus preventing cell damage in the first place. 
     Once the process has started though, Vit E and C scavanging has little 
to do with inflammation prevention.  Other cell mediators take over to 
attract more leukocytes, increase vasodilation, and breakdown dead or dying 
tissue.  To reduce inflammation you have to stop these other cellular 
products from being made by giving things like aspirin and steroids.  So in 
the end, free radical scavengers are good for preventative therapy, though 
there is still much debate upon how much good they really do.  Free 
radical damage is only one means of starting the events of inflammation. 
Once the cleanup cells get there, it is a whole other set of chemicals that 
perpetuates inflammation.  If the initial cells of inflammation 
(neutrophils) can't clean things up, then the inflammation becomes chronic, 
and event orchestrated by macrophages.  This can happen when free radical 
damage is continuous, like in the case of carbon tetrachloride exposure.  
The damage caused by the free radicals proceeds to chronic inflammation and 
eventual liver failure. If you want to know more about this there is a book 
called "Pathologic Basis of Disease" by Cotran, Kumar, and Collins.  It has 
lots of very technical information on the molecular events bihind disease. 
 Good luck         

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