Cadmium inhibits δ-aminolevulinate dehydratase from rat lung in vitro: Interaction with chelating and antioxidant agents

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• 作者：Cristiane Luchese ; Gilson Zeni ; Jo3 ; o B.T. Rocha ; Cristina W. Nogueira ; Francielli W. Santos
• 关键词：Cadmium ; &#x3b4 ; -ALA-D ; Chelating agents ; Antioxidant ; Selenium ; Lung
• 刊名：Chemico-Biological Interactions
• 出版年：2007
• 出版时间：30 January 2007
• 年：2007
• 卷：165
• 期：2
• 页码：127-137
• 全文大小：887 K

文摘

The effect of cadmium (Cd²⁺) on δ-aminolevulinate dehydratase (δ-ALA-D) activity from rat lung in vitro was investigated. δ-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd²⁺ in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)₂, and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelating × antioxidant agent) was also studied. Zinc chloride (ZnCl₂) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on δ-ALA-D activity. Cadmium inhibited rat lung δ-ALA-D activity at low concentrations. DTT (3 mM), but not ZnCl₂ (100 μM), protected the inhibition of enzyme activity caused by Cd²⁺. Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl₂ restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of δ-ALA-D inhibition induced by Cd²⁺. ZnCl₂ did not restore inhibition of enzyme activity caused by Cd²⁺ plus chelating agents. Conversely, DTT restored the inhibition induced by Cd²⁺/DMSA, but not by Cd²⁺/DMPS. Antioxidants were not effective in ameliorating δ-ALA-D inhibition induced by Cd²⁺, whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd²⁺ × DMPS × (PhSe)₂ and Cd²⁺ × DMPS × NAC was observed. There was no combined effect of Cd²⁺ × chelator × antioxidants when DMSA was used. This study demonstrated that Cd²⁺inhibited δ-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd²⁺ in rat lung.