EFFECTS IN WHOLE ANIMALS 725 



as an action mediated by peroxidase, the o-iodosobenzoate acting like hy- 

 drogen peroxide — furthermore, the taste of o-iodosobenzoate is almost 

 exactly like hydrogen peroxide. Injection of 10-20 //moles of o-iodosoben- 

 zoate into animals causes an immediate and marked depression of the res- 

 piration usually lasting 2-3 min, from which recovery occurs spontaneously. 

 o-Iodoxybenzoate is somewhat more potent but o-iodobenzoate is inactive. 

 Higher doses are required to elicit the circulatory depression described above 

 and the apnea is not secondary to the fall in blood pressure. Antagonism 

 between o-iodosobenzoate and cyanide on the respiration (the latter stim- 

 ulates respiration) is also observed and felt to support the concept that 

 o-iodosobenzoate acts by giving up its active oxygen. Jahn (1914) observed 

 rather nonspecific toxic effects in frogs, followed by a slowly developing 

 paralysis and loss of reflexes, death occurring when reflex activity has drop- 

 ped to zero and cardiac failure is evident. o-Iodobenzoate is less than one 

 tenth as toxic. The relative inactivity of o-iodobenzoate in all of these stud- 

 ies makes it very unlikely that any of the actions of o-iodosobenzoate are 

 due to the former compound, which undoubtedly is formed in the tissues. 

 Jahn postulated an enzyme that splits the iodine from o-iodobenzoate since 

 he found both organic and inorganic iodine in the urine after o-iodosoben- 

 zoate, the product presumably being salicylate. 



Very interesting effects on the blood are observed following intravenous 

 infusion of 0.5 millimole of o-iodosobenzoate into rabbits (Loevenhart and 

 Grove, 1911). Over a period of 3 days there is a slight depression of the 

 erythrocytes (around 15%) and negligible effects on coagulation mechanisms 

 but there appears early a very marked leucocytosis, this being confined 

 almost entirely to the polymorphonuclears, which increase from 2,160 to 

 11,362 in 24 hr. It is not known if this stems from a reaction with SH groups 

 or an action on some metabolic system. 



One factor which must be taken into account in considering the effects 

 of any SH reagent on the whole animal is the possible release of active 

 substances. Thus o-iodosobenzoate at fairly low concentrations (0.1 nxM) 

 releases catecholamines from the isolated chromaffine granules of the adrenal 

 medulla (D'lorio, 1957). This was thought to be an effect on the SH groups 

 located in the granule membranes, but there is no evidence for any mecha- 

 nism. On the other hand, the release of histamine from rat peritoneal mast 

 cells by Compound 48/80 is inhibited by o-iodosobenzoate, and presumably 

 histamine is not released by o-iodosobenzoate alone (VanArsdel and Bray, 

 1961). 



The intravenous lethal dose in rabbits is 150-200 mg/kg (0.57-0.76 milli- 

 mole/kg) and such values have generally been found in most animals. Dr. 

 Loevenhart courageously ingested a total of 1.3 g within 5.5 hr without 

 the slightest effect. The lethal dose of iodosobenzene is the same as that of 

 o-iodosobenzoate, indicating that the carboxylate group is not essential for 



