Effect of Mercuric Chloride Intoxication and Dimercaprol Treatment on σ‐Aminolevulinate Dehydratase from Brain, Liver and Kidney of Adult Mice

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Abstract
Dimercaprol is a compound used in the treatment of mercury intoxication, however with low therapeutic efficacy. It is assumed that dimercaprol acts by reactivating target sulfhydryl‐containing proteins. In the present investigation we studied the inhibitory effect of mercuric chloride treatment (3 days with 2.3 or 4.6 mg/kg HgCl2, sc) in mice on cerebral, renal and hepatic σ‐aminolevulinate dehydratase (ALA‐D) activity, and a possible reversal of the effect of mercury by dimercaprol (0.25 mmol/kg, 24 hr after the last mercury injection). Mercuric chloride did not inhibit cerebral ALA‐D at the doses injected. Dimercaprol treatment did not restore the normal enzyme activity of the liver after the 25% inhibition caused by 4.6 mg/kg HgCl2. In the kidney, dimercaprol enhanced the inhibitory effect of 4.6 mg/kg mercuric chloride (from 35% after mercury treatment alone to 65% after mercury plus dimercaprol treatment). Mercury content increased in kidney after exposure to 2.3 or 4.6 mg/kg and the levels attained were higher than in any other organ. Mercury accumulated in liver only after exposure to 4.6 mg/kg HgCl2, and dimercaprol further increased mercury deposition. Dimercaprol treatment also increased the levels of mercury in brain of animals exposed to 4.6 mg/kg HgCl2. The enzymes from all sources presented similar sensitivity to the combined effect of HgCl2and dimercaprolin vitro.In the absence of preincubation, 0‐500 μM dimercaprol potentiated the inhibitory effect of HgCl2on ALA‐D activity. In the presence of preincubation, and 100 and 250 μM dimercaprol enhanced ALA‐D sensitivity to mercury, whereas 500 μM dimercaprol partially protected the enzyme from mercury inhibition. Dimercaprol (500 μM) inhibited renal and hepatic ALA‐D when preincubated with the enzymes. These data suggested that the dimercaprol‐Hg complex may have a more toxic effect on ALA‐D activity than Hg2+. Furthermore, the present data show that dimercaprol did not act by reactivating mercury‐inhibited sulfhydryl‐containing ALA‐D, and that indeed it may have an inhibitory effectper sedepending on the tissue.

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