700 5. OXIDANTS 



Nephrotoxic Action 



Intravenous injection of around 0.5 g/kg of sodium tetrathionate into 

 dogs leads to the development of anuria within 30-60 min, a rapid reduc- 

 tion in creatinine clearance, and the appearance of proximal tubular ne- 

 crosis (Gilman et al., 1946). At the time of death there is no evidence of 

 toxicity, symptomatic or histological, in any other tissue from such min- 

 imally lethal doses; higher doses, however, can cause a long-lasting ataxia, 

 and in rabbits some difficulty in muscular relaxation. Inasmuch as simul- 

 taneous reduction of the tetrathionate to thiosulfate occurs, it was assumed 

 that the renal damage is related to the oxidation of SH groups, the toxicity 

 thus being related to that produced by the mercurials. Nevertheless, nephro- 

 toxic doses in rabbits do not inhibit kidney succinate dehydrogenase at aU 

 in vivo, and yet this enzyme is very sensitive to tetrathionate (Philips et al., 

 1947). Large doses of tetrathionate (1 g/kg of the sodium salt) in rabbits 

 lead to a 77% loss of glutathione in the kidneys, 28% in the blood, 30% 

 in the liver, and 20% in muscle after 90 min, most of the change occurring 

 within 30 min (Goffart and Fischer, 1948). These results might indicate that 

 tetrathionate has a greater effect on renal SH groups than those of other 

 tissues, without implying that the toxicity is due to the loss of glutathione. 



