Emanuelli T, Rocha J B, Pereira M E, Porciuncula L O, Morsch V M, Martins A F, Souza D O
Department of Chemistry, Santa Maria Federal University, RS, Brasil.
Pharmacol Toxicol. 1996 Sep;79(3):136-43. doi: 10.1111/j.1600-0773.1996.tb00257.x.
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.
二巯丙醇是一种用于治疗汞中毒的化合物，但其治疗效果较低。据推测，二巯丙醇通过使含巯基的靶蛋白重新活化而起作用。在本研究中，我们研究了氯化汞处理（以2.3或4.6mg/kg HgCl₂皮下注射3天）对小鼠脑、肾和肝δ-氨基-γ-酮戊酸脱水酶（ALA-D）活性的抑制作用，以及二巯丙醇（0.25mmol/kg，在最后一次注射汞后24小时）对汞作用的可能逆转。所注射剂量的氯化汞未抑制脑ALA-D。在由4.6mg/kg HgCl₂引起25%的抑制后，二巯丙醇处理未能恢复肝脏的正常酶活性。在肾脏中，二巯丙醇增强了4.6mg/kg氯化汞的抑制作用（从单独汞处理后的35%增加到汞加二巯丙醇处理后的65%）。暴露于2.3或4.6mg/kg后，肾脏中的汞含量增加，且达到的水平高于任何其他器官。仅在暴露于4.6mg/kg HgCl₂后，汞才在肝脏中蓄积，而二巯丙醇进一步增加了汞的沉积。二巯丙醇处理还增加了暴露于4.6mg/kg HgCl₂的动物脑中的汞水平。所有来源的酶在体外对HgCl₂和二巯丙醇的联合作用表现出相似的敏感性。在没有预孵育的情况下，0 - 500μM二巯丙醇增强了HgCl₂对ALA-D活性的抑制作用。在有预孵育的情况下，100和250μM二巯丙醇增强了ALA-D对汞的敏感性，而500μM二巯丙醇部分保护酶免受汞的抑制。当与酶预孵育时，二巯丙醇（500μM）抑制肾和肝ALA-D。这些数据表明，二巯丙醇 - 汞复合物对ALA-D活性可能比Hg²⁺具有更大的毒性作用。此外，目前的数据表明，二巯丙醇并非通过使受汞抑制的含巯基ALA-D重新活化而起作用，实际上，根据组织不同，它本身可能具有抑制作用。
