ACTIVE TRANSPORT 705 



Some information on the mechanism by which arsenite acts on H+ trans- 

 port may be found in the work of Davenport. Arsenite inhibits acid secretion, 

 causes accumulation of pyruvate (Davenport and Jensen, 1949), but does 

 not bring about detectable reduction of lipoate (Davenport et al., 1956). 

 By the technique described (page 1-504) and illustrated (Fig. 1-10-6), it 

 was found that arsenite markedly lowers the threshold for 2, 4-dinitro phenol 

 action (Davenport, 1955). The threshold is normally around 0.01 mM and 

 arsenite lowers it to near 0.001 mM at a concentration which inhibits only 

 20%; this implies that arsenite inhibits the generation of ATP rather than 

 interfering with its utilization, so the balance of evidence here points to 

 the primary mechanism of transport inhibition being an inhibition of pyru- 

 vate oxidation. 



Effects on the Kidneys 



Studies on the toxicology of the arsenicals have shown that the kidney 

 glomeruli and tubules may be to varying degrees directly damaged; renal 

 function may be further disturbed by fluid and electrolyte imbalances. 

 The first effect is perhaps a dilatation and swelling of the glomerular capil- 

 laries, followed by progressive tubular necrosis. The increased permeability 

 of the glomerular capillaries leads to the proteinuria frequently observed. 

 Some species, such as dogs and rabbits, may succumb to the renal lesions 

 when organic arsenicals are administered (Gruhzit, 1935). Bunting and 

 Longley (1940) made a thorough study of the renal changes brought 

 about by tryparsamide in the rat. Rats were given increasing doses intra- 

 venously: 1 g/kg, which is half the tolerated dose, the first week; 1.5 g/kg 

 during the second week; 2 g/kg during the third week; and 3 g/kg by the end 

 of the month. The most prominent lesion 24 hr after the initial dose is a 

 coagulative necrosis of the cells of the convoluted tubules with the appear- 

 ance of pycnotic nuclei; if high doses are given initially, changes occur 

 within 1 hr. The ascending limb shows the greatest damage. Glomerular 

 injury is slight, but tryparsamide is known not to be a capillary depressant 

 to the degree that the trivalent arsenicals are. At the end of the month there 

 is no necrosis and the tubules are lined with mature epithelium, indicating 

 the development of resistant cells (see page 765). The site of injury in- 

 dicates the concentration of the arsenical during resorption to be the im- 

 portant factor, rather than a special sensitivity of these cells. Lewisite 

 given intravenously produces glomerular congestion and cloudy swelling 

 of the tubules within 1 hr, and tubular necrosis after 24 hr (Cameron 

 et al., 1946). It is somewhat surprising that the urine volume decreases 

 in arsenical poisoning (Von Boeck, 1871; Araki, 1893; Jastrowitz, 1908) 

 since other SH reagents, such as the mercurials, usually produce diuresis, 

 and there appears to be no particular inhibition of ion and water resorption 

 by the arsenicals. Much of the oliguria might be due to obstructive swelling 



