954 7. MERCURIALS 



indicated by the fact that administration of dimercaprol is not remarkably 

 successful, although certain clinical improvement has been noted (Bivings 

 and Lewis, 1948). 



Histological Changes 



The neurological picture of fasciculations, hyperreflexia, tremor, and mo- 

 tor weakness, followed by muscular atrophy, often seen in chronic poison- 

 ing with the organic mercurials — as reported, for example, by Kantarjian 

 (1961) in individuals eating bread treated with the fungicide Granosan M 

 (ethylmercuri-p-toluene sulfonanilide) — accompanied by occasional numb- 

 ness or paresthesias, may clinically resemble amyotrophic lateral sclerosis 

 (Brown, 1954). Rats and monkeys chronically poisoned with MM show 

 Wallerian degeneration of the peripheral nerves (Hunter et al., 1940). The 

 peripheral nerves and the posterior spinal roots are affected first, and later 

 the posterior columns and granular layer of the middle lobe of the cerebel- 

 lum. The ataxia and tremor could result from the cerebellar lesions. Bila- 

 teral cortical atrophy in the area striata was associated with the reduction 

 of the visual field. A good review of the neurological changes has been pro- 

 vided by Noe (1960). The renal and intestinal changes have been described, 

 and we shall only note that degeneration of the liver has also been observed 

 (MacNider, 1918 b). Dogs given HgClg orally (15 mg/kg) exhibit a deposi- 

 tion of fat in the cells surrounding the central vein, followed by cloudy 

 swelling and necrosis, with eventual extension to the periphery of the lobule. 

 Such hepatic changes could well be responsible for some of the over-all 

 metabolic disturbances observed in animals. 



Foulerton (1921) believed that Hg++ has an affinity for lipids, not only 

 because of the solubility of HgClg in fat but also due to the formation of 

 oleates, and is transported to the liver in the circulating blood fat. The liver 

 damage then results in a defective lipid metabolism. There are certainly 

 definite disturbances in lipid metabolism — for example, Ogilvie (1932) 

 found an immediate and considerable rise in blood lipid following adminis- 

 tration of HgCla; subsequently there is a fall and a second rise — but no 

 evidence to indicate the mechanism involved. Toxic doses of mersalyl in 

 rats produce hypoglycemia and reduce the liver glycogen to essentially zero 

 (Dzurik et al., 1963). It was stated that these effects are secondary to renal 

 dysfunction and not a manifestation of a direct action of the mercurial on 

 the tissues, but this seems unlikely and there are possibly several factors 

 of importance, including epinephrine release as a result of a nonspecific 

 stress reaction. Free amino acids in the livers of rats given HgClg for 10 

 days were determined by Thoelen and Pletscher (1953), and it was shown 

 that although serine, leucine, and phenylalanine do not change significantly, 

 cystine rises to 3 times the control value. This was interpreted as a detoxi- 

 fication response. One must question the ability of animals to increase the 

 synthesis of specific amino acids for the purpose of complexing with a non- 



