2,3-Dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase mercury- and cadmium-induced inhibition of δ-aminolevulinate dehydratase

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• 作者：Nogueira ; C.W. ; Soares ; F.A. ; Nascimento ; P.C. ; Muller ; D. ; Rocha ; J.B.T.
• 关键词：δ ; -Aminolevulinate dehydratase ; DMPS ; DMSA ; Cadmium ; Mercury ; Lead ; Zinc ; Phorphibilinogen synthase ; δ ; -ALA-D
• 刊名：Toxicology
• 出版年：2003
• 出版时间：March 3, 2003
• 年：2003
• 卷：184
• 期：2-3
• 页码：85-95
• 全文大小：206 K

文摘

Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), are becoming common agents for treating humans exposed to heavy metals. Heavy metals such as Pb²⁺, Hg²⁺ and Cd²⁺ can inhibit δ-aminolevulinate dehydratase (δ-ALA-D) activity. δ-ALA-D catalyzes the condensation of two δ-aminolevulinic acid (δ-ALA) molecules with the formation of porphobilinogen, a heme precursor. The effects of DMSA and DMPS alone or in combination with Cd²⁺, Hg²⁺, or Pb²⁺ on hepatic δ-ALA-D were examined. DMPS and DMSA caused a dose-dependent inhibition of hepatic δ-ALA-D. In the presence of Hg²⁺ or Cd²⁺ the inhibitory potency of DMPS increased. Similarly, the inhibitory effects of Hg²⁺ and Cd²⁺ were markedly increased in the presence of DMSA. In contrast, the inhibitory effect of DMPS was not changed by inclusion of Pb²⁺. As observed with DMSA, Zn²⁺ did not modified the inhibitory effect of DMPS. Data of the present report support the idea that the complexes formed (metals–DMSA or DMPS) were more inhibitory than the metal (Hg²⁺ and Cd²⁺) or the chelating agent alone to the hepatic δ-ALA-D activity, in vitro. The mechanism of hepatic δ-ALA-D inhibition by Hg²⁺–DMPS/DMSA and Cd²⁺–DMPS/DMSA complexes involve the essential thiol groups of the enzyme.