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

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 delta-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 HgCl2 and dimercaprol in vitro. In the absence of preincubation, 0-500 muM dimercaprol potentiated the inhibitory effect of HgCl2 on ALA-D activity. In the presence of preincubation, and 100 and 250 muM dimercaprol enhanced ALA-D sensitivity to mercury, whereas 500 muM dimercaprol partially protected the enzyme from mercury inhibition. Dimercaprol (500 muM) 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 acts by reactivating mercury-inhibited sulfhydryl-containing ALA-D, and that indeed it may have an inhibitory effect per se depending on the tissue.

Role of Selenium in Mercury Intoxication in Mice

“…This also gets support from the fact that selenium blocks the effects of chelating agents in mercury intoxication and the process may be holding good for elimination of mercury from the body in natural course leading to higher accumulation of mercury in the body organs 43) . Our results show high mercury accumulation in kidney than in liver, which is also supported by the other studies 2,4,12,48) . Enhancement of GSH level may be towards the defense mechanism against the effect of ROS in the cell, which was found to be more in selenium post treated animals in liver and kidney tissues rather than its pre treatment.…”

“…The kidney, liver, gastrointestinal system, and central nervous system are the main target sites of mercury toxicity 3) . The primary target organ for inorganic salts of mercury is the kidney hence it is known as nephrotoxic agent 2,4) . Because of the high bonding affinity between mercury and sulfur, mercury binds to metallothioneins and small molecular weight thiols such as cysteine 5) and glutathione 6) .…”

The cytotoxicity of mercury chloride to the keratinocytes is associated with metallothionein expression

“…Heavy metals such as mercury (Hg), which is added to skin-whitening cosmetics, may cause acute or chronic damage to human cells. Hg, a divalent metal with no known biological function, may cause several deleterious effects in adults (1,2), as well as in developing organisms (3,4), which primarily involve the central nervous system (5-7) and the kidneys (1,8,9). Young animals seem to be more sensitive to Hg toxicity than adults, particularly during the first days following birth.…”

Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

“…4.2.1.24). ALA-D is a sulfhydryl-containing enzyme that is inhibited by heavy metals and sulfhydryl reagents (10)(11)(12)(13)(14)(15)(16) and seems to be the principal leadbinding protein in human erythrocytes (17). The toxic effects of aluminum on ALA-D may involve protein synthesis, enzyme inhibition or enzyme activation (18).…”