692 6. ARSENICALS 



the administration of arsenite to eight human subjects for 10 days led to 

 a mean increase of 26 mg% in free cholesterol and 44 mg% in total choles- 

 terol in the blood, and Mookerjea and Sadhu (1955) found marked increases 

 in both free and esterified cholesterol in the kidneys of rats given arsenite 

 for 3-4 weeks, although the changes in the liver and blood are much less. 

 It may well be that in these experiments the low tissue concentration of 

 arsenite led to a diversion of two-carbon fragments to sterol synthesis 

 as a result of the inhibition of the cycle, and that higher arsenite concen- 

 trations would have depressed the formation of the sterols. 



Much less is known about the effects of arsenicals on phospholipid 

 metabolism, but Cantrell (1951) found that trypanosomes isolated from 

 rats treated with oxophenarsine exhibit an impaired incorporation of labeled 

 phosphate into phospholipids; since glucose utilization is unaffected, he 

 postulated that the arsenicals may well act primarily on lipid metabolism 

 in these organisms. However, Mazelis and Stumpf (1955) reported that 

 arsenite does not affect the incorporation of labeled phosphate into phos- 

 pholipids in peanut mitochondria with succinate as the substrate. More 

 work must be done in this field before conclusions can be drawn, and might 

 be profitable in the light of the recently discovered functional significance 

 of some of the phosphohpids. 



Nitrogen Metabolism 



Arsenicals may also affect protein and amino acid metabolism either 

 directly or indirectly, and the relations are so complex that the resultant 

 changes in the nitrogenous constituents of the whole animal are difficult 

 to interpret. The earliest workers found little effect of subtoxic doses of 

 arsenite on protein metabolism or urinary nitrogen excretion in fasting dogs 

 or dogs in nitrogen balance (Von Boeck, 1871; Fokker, 1872). However, 

 Pribyl (1927) noted quite definite changes in rabbits given arsenite orally 

 in increasing dosage over 10 days (see accompanying tabulation). It is 

 clear that the rises in blood and urinary nitrogen are almost entirely due 



