Efeito do cádmio sobre a enzima d-aminolevulinato desidratase de pulmão de ratos in vitro: interação com agentes quelantes e antioxidantes

• Ano de defesa: 2007
• Autor(a) principal: Luchese, Cristiane
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; BR; Bioquímica; UFSM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
• Palavras-chave em Português: Cádmio; D-ALA-D; Agentes quelantes; Antioxidantes; Pulmão; Cadmium; Chelating agents; Antioxidants; Lung; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/11169

The exposure of human populations to a variety of heavy metals has been a public health concern. Cadmium is a non-essential elements due to its immense usage in various industrial applications, is an environmental contaminant with food and tobacco smoking. This toxic metal is more efficiently absorbed through the lungs than through the gastrointestinal tract. Therefore, the use of lung as a target tissue of cadmium exposure is of great importance because this heavy metal can be absorbed on suspended particles, entering the lung through the respiration. Thus, a possible therapy for metal intoxication is to remove the toxic metals from the bound functional bioligands. The present study was designed to evaluate the effect of cadmium on d-minolevulinate dehydratase (d-ALA-D) activity from rat lung in vitro. d-ALA-D activity, a toxicological parameter, has been reported as a target of cadmium 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 agent (ascorbic acid, diphenyl diselenide, (PhSe)2, and Nacetylcysteine (NAC)) were also evaluated; as well as, the effect of a combined therapy (dithiol chelating x antioxidant agent) was studied. Moreover, to investigate the possible mechanism involved, we determined the effect of zinc chloride (ZnCl2) and dithiothreitol (DTT). The rat lung d-ALA-D activity was inhibited by low concentrations of cadmium, this inhibition occurred due the oxidation of SH groups of enzyme, and not by displacing zinc from the enzyme structure. The chelating agents were not effective in restoring enzyme activity inhibited by cadmium, and it presented an inhibitory effect per se. The possible mechanism involved in this inhibition was demonstrated. DTT restored the inhibition caused by both chelating agents, but ZnCl2 restored only the inhibitory effect of DMSA. This indicated that DMPS did not remove the zinc ions of the enzyme structure. This study also demonstrated that these chelating agents potentialized the d-ALA-D inhibition caused by cadmium. In this way, the study of possible mechanism verified that DTT restore the enzyme inhibition caused by cadmium/DMSA complex, but not by cadmium/DMPS complex. In contrast to DTT, ZnCl2 did not restore the enzyme activity inhibited by both complexes. In relation to antioxidants compounds, we can verify that none antioxidant utilized in this work was efficient in restoring the enzyme activity inhibited by cadmium. Some authors had demonstrated that the association of chelating and antioxidant agents is a good alternative in treatment of metal intoxication. In this way, we observed a combined effect of cadmium x DMPS x (PhSe)2 and cadmium x DMPS x NAC. However, this combined effect of cadmium x antioxidant x chelating did not observe when we utilized DMSA as chelating agent. In general, the results of this study indicate that cadmium inhibited the pulmonary d-ALA-D activity; and, the use oh chelating and antioxidant agents, alone or combined, 6 did not restore the enzyme activity, in some cases, potentialized the inhibition induced by cadmium. The principal mechanism involved in enzyme inhibition was the oxidation of SH groups.