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What Oxidant Compounds Are Useful Medicinally ? 
By What Mechanism(s) Do They Function As Medicinal Oxidants?

~~~   LISTS  OF  CLINICALLY  USEFUL  OXIDANTS   ~~~
Inorganic Oxidants: 
  hyperbaric oxygen (O2), singlet oxygen (O2), 
  ozone (O3), hydrogen peroxide (H2O2), 
  magnesium peroxide (MgO2), zinc peroxide (ZnO2), 
  chlorine dioxide (ClO2), chlorite (ClO2-), 
  nitrate (NO3-), permanganate (MnO4-), iodine (I2)  
Organic Oxidants: 
  organic ozonides (RO3R'), organic peroxides (ROOR'), 
  quinones (Q), alphaketoaldehydes (RCOCHO), 
  imidazoles, methylene blue 
Sufur Compounds: 
  disulfides (RSSR'), sulfoxides (RSOR'), 
  disulfide monoxides (RSSOR') 
Ultraviolet Light 

	~~~  INORGANIC  PEROXIDES  ~~~

	Hydrogen peroxide   (H2O2)
	Magnesium peroxide  (MgO2)
	Zinc  peroxide      (ZnO2)

Peroxides of cationic metals yeild hydrogen peroxide 
upon neutral or acid hydrolysis.
	XO2   +   2H+   --->   X++   +   H2O2 

Three main mechanisms exist whereby H2O2
may deplete hydrogen from available carriers.
	1.  glutathione peroxidase system
	2.  mitochondrial cytochromes
	3.  nonspecific peroxidases

    ~~~  GLUTATHIONE  PEROXIDASE  SYSTEM  ~~~

This BETS starts with sugar as the original [H] donor 
and ends with HOOH or LOOH as the final [H] acceptor. 
	G6P ... NADP+/NADPH ... FAD/FADH2 ... 
	GSSG/GSH ... cys-Se/cys-SeH ... LOOH/LOH+HOH 

Note that when all components are present, 
this BETS can function as an efficient depletor 
of reductants from the NADPH and GSH pools. 

Sugars, NADPH, or GSH might otherwise be useful for 
syntheses and support the proliferation of pathogens. 

Blockade by cysteine deficiency, by selenium deficiency, 
or by mercury toxicity inhibit the function of this BETS. 

~~~ RESPIRATORY CYTOCHROMES AS ACTIVATORS OF H2O2 ~~~

The cytochromes are ferroporphyrin containing proteins
which sequentially carry electrons in the mitochondria.

Cytochrome a3 contains both iron and copper cations and 
is activated by diatomic oxygen or by hydrogen peroxide.

The respiratory electron transport chain 
can be abbreviated as follows:

Krebs Cycle ... NAD+/NADH ... FMN/FMNH2 ... CoQ/CoQH2 
... cytB-Fe+++/cytB-Fe++ ... cytC-Fe+++/cytC-Fe++ 
... cytA-Cu++/cytA-Cu+ ... O2/HOH or HOOH/HOH

O2 or H2O2 activate cytosol to mitochondrial shuttles:

NADH ... DHAP/G3P ... FAD/FADH2 ... CoQ/CoQH2 ...

~~~   AUTOREGENERATION   OF   HYDROGEN   PEROXIDE   ~~~

1)  Hydrogen peroxide attaches to the active center 
    of peroxidase. 
	HOOH   +  P    --->  P** 
2)  One hydrogen atom is abstracted from a divalent 
    hydrogen carrier. 
	2HXH   +  P**  --->  2(HX*)  +  P  +  2HOH 
3)  The radicalized donors are oxidatively quenched 
    by diatomic oxygen. 
	2(HX*)   +  2OO  --->  2X  +  2(-OO*)  +  2H+ 
4)  Superoxide is dismutated or reduced. 
	2(-OO*)  +  2H+  --->  OO  +  HOOH 
	(-OO*) + AOH + H+  --->  AO*  +  HOOH 

The HOOH produced in 4) can restart 
  the process as in 1) repeatedly. 
By cancelling out all substances which appear 
  on both sides of these equations, the overall 
  effect is shown below. 
	2HXH   +  OO   --->  2X  +  2HOH 
According to this composite equation the overall 
  effect is to dehydrogenate large quantities 
  of divalent reductants. 
A non-mitochondrial consumption of one molecule 
  of diatomic oxygen occurs with each cycle. 
Thus low dose administration of HOOH can have 
  a profound oxidative impact by this mechanism. 

	~~~   ALDEHYDE   REACTIONS   ~~~
Aldehydes can reversibly add to thiols and to amines and 
therefore be stored or carried covertly and indefinitely. 

   H                         H
R--C==O  +  R'--SH  <---> R--C--OH
                             SR'

   H                         H              H
R--C==O  +  R'--NH2 <---> R--C--OH <---> R--C==NR' + H2O
                            HNR'

In the hydrated form aldehydes are dehydrogenated 
by aldehyde oxidases.
            
   H                      H
R--C==O  +  HOH  --->  R--C--OH  - 2 [H]  --->  R--C==O
                          OH                       OH 

	~~~  ALDEHYDES  AS  PRO-OXIDANTS  ~~~
Aldehyde oxidases catalyze the following reaction: 
    RCHO  +  H2O  +  2 O2  --->  RCOOH  +  2 -OO*  +  2 H+ 
Their mechanism can be represented by the following BETS: 
    RCOOH/RCHO ... Mo(+6)/Mo(+5) ... FAD/FADH* ... 
    Fe(+3)/Fe(+2) ... O2/-OO* 
The superoxide produced can be dismutated: 
    -OO*  +  -OO*  +  2 H+  --->  O2  +  HOOH
The superoxide can also be reduced by ambient antioxidants: 
    -OO*  +   H+   --->  HOO*
    HOO*  +   AOH  --->  AO*  +  HOOH
Note that in either case hydrogen peroxide is produced. 
Thus superoxide, hydroperoxyl radical, and hydrogen peroxide 
    are produced when aldehyde are oxidized. 
These oxidants would consume [H] and: 
 1) at very low doses might activate the immune system, 
 2) at low doses inhibit the growth of pathogens, 
 3) at higher doses cause oxidative damage. 

	~~~ FORMATION AND HYDROLYSIS OF OZONIDES ~~~

                       /O\          O   O           O-O
                      O   O         O  ||          /   \
OOO + R-C==C-R' --> R-C---C-R'--> R-C + C-R'--> R-C     C-R'
        H  H          H   H         H   H         H \O/ H

        O    O          OH      O                H   O
        O   ||          O      ||                O  ||
HOH + R-C +  C-R' --> R-C-OH +  C-R' --> R-C=O + O + C-R'
        H    H          H       H          H     H   H

    O-O  + HOH     OH            OH     O               H   O
   /   \           O   OH        O     ||               O  ||
R-C     C-R' --> R-C-O-C-R'--> R-C-OH + C-R'--> R-C=O + O + C-R'
  H \O/ H          H   H         H      H         H     H   H

Note that upon hydrolysis by either mechanism, 
  for each molecule of ozonide present there is produced: 
  one molecule of hydrogen peroxide plus two aldehydes. 

~~~ ORGANIC HYDROPEROXIDES AS HYDROGEN ACCEPTORS ~~~

Organic hydroperoxides (ROOH) can consume reducing 
  equivalents along the glutathione peroxidase BETS. 
	G6P  ...  NADP+/NADPH  ...  FAD/FADH2  ... 
	GSSG/GSH ... cys-Se/cys-SeH ... ROOH/ROH+HOH 
Polyunsaturated fatty acids which have undergone 
  lipid peroxidation can activate this sequence. 
Also the "ene reaction" of PUFA's with singlet oxygen 
  produces lipid hydroperoxides. 
In research certain organic hydroperoxides are often 
  used as oxidant probes, namely: 
		- tertiary butyl hydroperoxide 
		- cumene hydroperoxide 
		- benzoyl peroxide 

		~~~  OXIDES  OF  CHLORINE  ~~~
1)  The element chlorine can occur in various 
    oxides and valences as follows: 
Cl2    Cl-    ClO-     ClO2-    ClO2    ClO3-    ClO4- 
2)  The chloride oxides can release one atom of oxygen 
    which strongly abstracts two hydrogen atoms 
    from numerous donors: 
  XH2   +   ClO-   --->   X   +   Cl-   +   H2O 
3)  The chlorine oxides are so strong they can 
    turn hydrogen peroxide into singlet oxygen: 
  HOOH  +   ClO-   --->   O==O   +   Cl-   +   H2O 
4)  Myeloperoxidase physiologically produces 
    hypochlorite from hydrogen peroxide: 
  HOOH   +   Cl-   --->   ClO-   +   HOH 
5)  Electrolysis of saline produces hypochlorite: 
cathode:  2 e-  +  2 H2O   --->  H2  +  2 OH- 
anode:    2 Cl-  -  2 e-   --->  Cl2 
  Cl2   +   2 OH-   --->   Cl-   +   ClO-   +   H2O 
6)  Chlorite in acid solution produces chlorine dioxide: 
  4 HClO2 ---> 2 ClO2  +  ClO3-  +  Cl-  +  2H+  +  H2O 
7)  Chlorine dioxide in alkaline solution produces: 
  2 ClO2   +   2 OH-   --->  ClO2-   +   ClO3-   +  H2O 
                
	~~~ SULFUR COMPOUNDS AS WEAK OXIDANTS ~~~
ELEMENTAL  SULFUR:
	S8   +   16 GSH   --->   8 H2S   +   8 GSSG 
ORGANIC  DISULFIDES  (e.g. products of other oxidants):
	RSSR  +   2 GSH   --->   2 R-SH  +   GSSG 
DIALKYL  SULFOXIDES  (e.g. DMSO):
	RSR   +   2 GSH   --->   RSR  +  H2O  +  GSSG 
	 O 
DISULFIDE  MONOXIDES (e.g. allicin):
	RSSR  +   4 GSH   ---> 2 RSH  +  H2O  +  2 GSSG 
	 O 

	~~~  ANODIC  OXIDATION  AS  THERAPY  ~~~
Electrolysis using direct current has been studied
  for its growth stimulating and antitumor effects.
One of the most interesting applications of this
  has been the work of Bjorn E. W. Nordenstrom, 1983,
  "Biologically Closed Electric Circuits",pp 269-317
Using precisely calibrated direct current applied
  to silver electrodes surgically placed within tumors,
  regressions are readily and repeatably produced.
As expected from bioelectronic theory,
  the positively charged electron collecting anode
  is the pole applied to the tumors.
Four theories can be advanced to explain this:
 1) anodic oxidation of electron/hydrogen carriers
 2) electrolysis of water producing acid (H+)
 3) release of focally toxic silver cation (Ag+)
 4) conversion of chloride (Cl-) to chlorine (Cl2)

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