706 6. ARSENICALS 



of the glomerular capillaries and tubules, but the reduction of the blood 

 volume and blood pressure may also contribute. Eenal transports in isolated 

 preparations have been shown to be depressed (Table 6-9), but it should 

 be noted that in most of this work, especially with regard to the ions, 

 transtubular transport is not determined but presumably only the intra- 

 cellular exclusion of Na+ and accumulation of K+. The immediate effects 

 from subtoxic doses of the arsenicals on these important renal transports 

 in vivo have never been investigated. 



TISSUE FUNCTIONS 



The effects of the arsenicals on certain tissues will be discussed in this 

 section, not only because of the importance of attempting to correlate 

 functional and metabolic changes, but in order to provide a basis for under- 

 standing some of the toxic effects in arsenical poisoning. 



Nervous System 



It is surprising, in view of the metabolic actions of the arsenicals, that 

 central nervous system effects are generally minimal and have often not 

 even been mentioned in toxicological studies, since the nerve cells depend 

 on pyruvate oxidation and the cycle for their energy supply. A characteris- 

 tic result of chronic poisoning is peripheral neuritis, but central function 

 is little disturbed. In acute poisoning there may be respiratory depression, 

 which could arise from an action on the central respiratory pathways, and 

 terminal convulsions, but these latter are more probably anoxic in origin. 

 The specific effects of the pentavalent arsenicals on the optic nerve will 

 be discussed later (page 716). Most workers would probably argue that the 

 lack of central effect is due to poor penetration of the arsenicals into the 

 brain or the nerve cells, and certainly the asenicals occur in the brain in 

 lower concentration than in most other tissues (page 780). Morishima 

 (1900 a) observed that arsenite given by intracerebral injection to rabbits 

 is much more toxic than by other routes, and that the animals exhibit 

 marked paralysis and no diarrhea. Koppanyi and Sperling (1947) found 

 that neither arsenite nor dimercaprol produces central effects at certain 

 dosage levels, but when rabbits receive dimercaprol intramuscularly and 

 arsenite 10 min later intravenously there is rapid development of motor 

 excitation and parasympathetic stimulation. This might be due to the 

 greater lipid solubility of the arsenite-dimercaprpl complex and conse- 

 quently its rapid penetration into the central nervous system. However, 

 in the light of certain enzyme responses to mixtures of arsenite and dimer- 

 caprol (page 645) and the fact that injection of the complex into rabbits 

 does not produce these effects, it might be well to be cautious in interpreting 

 these results. 



