Kachru D N, Khandelwal S, Tandon S K
Industrial Toxicology Research Centre, Lucknow, India.
Biomed Environ Sci. 1989 Sep;2(3):265-70.
The influence of methionine supplementation on the efficacy of common antidotes to lead poisoning, calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) and D-penicillamine (DPA), was investigated in rats. The animals were given lead acetate (0.1% in drinking water) for 12 weeks and thereafter treated with CaNa2EDTA. DPA (0.3 mmol/kg, intraperitoneally), DL-methionine (1.34 mmol/kg, intragastrically), or the combination of a chelating agent and methionine for 3 days. While chelating agents enhanced the urinary excretion of Pb, methionine increased the fecal excretion of Pb significantly. Treatment with the combination of a chelating agent and methionine did not potentiate the effect of each antidote. However, methionine supplementation increased the efficacy of both chelating agents in reducing the hepatic and renal Pb burden but not the blood Pb level. The Pb-induced inhibition of blood delta-aminolevulinic acid dehydratase activity and the increase in urinary excretion of delta-aminolevulinic acid were reversed to a certain extent by CaNa2EDTA, DPA, and methionine but the combination did not improve their individual performances. The beneficial effects of methionine may be attributed to its ability to increase the bioavailability of glutathione (GSH), useful in chelating Pb and counter-acting the toxic effects, as evidenced by restoration of the Pb-induced decrease in hepatic GSH level by treatment with methionine. Methionine may be useful as a supportive therapy in chelation of Pb.
在大鼠中研究了补充蛋氨酸对铅中毒常见解毒剂乙二胺四乙酸二钠钙(CaNa2EDTA)和D-青霉胺(DPA)疗效的影响。给动物饮用含0.1%醋酸铅的水12周,之后用CaNa2EDTA、DPA(0.3 mmol/kg,腹腔注射)、DL-蛋氨酸(1.34 mmol/kg,灌胃)或螯合剂与蛋氨酸的组合进行治疗,为期3天。虽然螯合剂可增加尿铅排泄,但蛋氨酸显著增加了粪铅排泄。螯合剂与蛋氨酸联合治疗并未增强每种解毒剂的效果。然而,补充蛋氨酸提高了两种螯合剂减轻肝脏和肾脏铅负荷的疗效,但对血铅水平无此作用。CaNa2EDTA、DPA和蛋氨酸在一定程度上逆转了铅诱导的血δ-氨基-γ-酮戊酸脱水酶活性抑制及尿δ-氨基-γ-酮戊酸排泄增加,但联合使用并未改善它们各自的效果。蛋氨酸的有益作用可能归因于其增加谷胱甘肽(GSH)生物利用度的能力,GSH有助于螯合铅并对抗毒性作用,蛋氨酸治疗可恢复铅诱导的肝脏GSH水平降低,这证明了这一点。蛋氨酸可能作为铅螯合治疗中的一种支持性疗法有用。