696 5. OXIDANTS 



Hydrogen peroxide is by no means the ideal glycolytic inhibitor for this 

 type of work. 



Effects on Tissue Function and in Whole Animals 



The spontaneous motility of the rat intestine is extremely sensitive to 

 hydrogen peroxide inasmuch as 10% stimulation of the amplitude occurs 

 with 0.00057 mikf (Goodman and Hiatt, 1964). At 0.057 mM hydrogen per- 

 oxide the stimulation of contraction by acetylcholine is blocked and 67% 

 of the total SH groups of the tissue are reacted. Although hydrogen per- 

 oxide at 0.001 vaM has no definite effect on the spontaneous contractility, 

 it reduces the effect of acetylcholine somewhat. Other SH reagents act sim- 

 ilarly and it appears that the response to acetylcholine is dependent on 

 SH groups. The contractility of nonconducting rabbit psoas muscle is block- 

 ed by 300 mM hydrogen peroxide after 7 min exposure, and this is not 

 reversible with cysteine (Korey, 1950). However, little can be learned from 

 concentrations of this magnitude. 



An interesting relationship was discovered by Feinstein et al. (1954), in 

 that a sublethal dose of iodoacetate (20 mg/kg) and a 20% fatal dose of 

 hydrogen peroxide (15 meq/kg) given together kill all the animals. Inas- 

 much as iodoacetate also potentiates the lethality of X-irradiation in mice, 

 this was considered as evidence that radiation may produce some of its 

 effects by the release of hydrogen peroxide. It was noted that the toxicity 

 of hydrogen peroxide is markedly increased by treating the animals with 

 azide, a catalase inhibitor; however, hydroxylamine, which is a better cat- 

 alase inhibitor, does not augment the effects of hydrogen peroxide. 



TETRATHIONATE 



Tetrathionate appears to be a fairly specific oxidant for SH groups under 

 the proper conditions, but has been used very little in enzyme work. It was 

 found to be capable of antagonizing cyanide poisoning in dogs at doses of 

 500 mg/kg (Chen et al., 1934), and today we might interpret this as due to 

 methemoglobin formation. Tetrathionate has been used in a method for 

 the determination of protein methionine, which is demethylated to homo- 

 cysteine and then oxidized (Baernstein, 1936). It has been used clinically 

 in thromboangiitis obliterans, supposedly for an effect on the blood, an in- 

 crease in the oxygen capacity being observed (Theis and Freeland, 1940). 

 It is surprising that the blood glutathione increases after injection of tetra- 

 thionate. It has been applied occasionally to the reduction of the cytochrome 

 components of the respiratory chain, since the initial work of Keilin and 

 Hartree (1940), the tetrathionate apparently being oxidized to sulfite. It is 

 thus, like hydrogen peroxide, both an oxidant and a reductant, which makes 



