Hee S S, Igwe O J, Boyle J R
Kettering Laboratory, Department of Environmental Health, University of Cincinnati Medical Center, OH 45267-0056.
Biol Trace Elem Res. 1988 Dec;18:9-28. doi: 10.1007/BF02917485.
Trace elements participate in the organ specific impact of 1,2-dichloroethane (EDC) and Disulfiram (tetraethylthiuram disulfide; Antabuse (DSF] administered singly or together, on male Sprague-Dawley rats exposed by diet (AIN-76) to DSF (0 and 0.15% for 10 d before and during exposure to EDC) and by inhalation to EDC (0, 153, 304, 455 ppm (v/v); 7 h/d for 5 d/wk for 30 exposure days). Kidney, liver, spleen, and testes at exposure d 30 as well as progressive urine samples were examined for elemental content by simultaneous inductively coupled plasma atomic emission spectroscopy. Each compound singly or together produced EDC dose related (r greater than or equal to 0.8) changes in metal content in organs relative to controls. There were increases induced by EDC alone for P and Sr in the liver and decreases for Fe, Mg, and P in the spleen. EDC in DSF-exposed animals caused increases in Ca, Cu, Fe, Mn, and S and a decrease in K in the liver; increases in Ca, Cu, Fe, Mn, Mo, P, and S and a decrease of Zn in the testes; an increase in Fe and a decrease in K in the spleen; and an increase of P in the kidney. DSF alone increased Cu in the liver but decreased it in the testes and kidney; Pb was increased in the liver and kidney and Zn in the liver, spleen, and kidney; Al and Si were increased also in the liver, S in the spleen, and K in the kidney; Mn and Na were decreased in the kidney. The organs showing histopathology (the liver and testes) both showed increases in Ca, Cu, Fe, Mn, and S. Metals in urine characterized a "shock" impact of the initial exposure by initial excretion of Na and retention of most other elements. After steady state (greater than 12 d), EDC alone caused increases for Sr and Zn; for EDC-DSF, EDC also decreased Na in addition to the changes elicited by DSF alone (increases in S and Zn and a decrease for Cu). The results were interpreted from the perspective of the effects of metals on the glutathione detoxicative pathway, the concentration of free diethyldithiocarbamate in urine, and an interaction with bone. Mechanisms of action of EDC, DSF, and EDC-DSF must include consideration of trace elements in addition to organic intermediates, metabolites, and enzymes.
微量元素参与了1,2 - 二氯乙烷（EDC）和双硫仑（二乙基二硫代氨基甲酸钠；戒酒硫（DSF））单独或联合给药对雄性Sprague - Dawley大鼠的器官特异性影响。这些大鼠通过饮食（AIN - 76）接触DSF（在接触EDC之前和期间，剂量分别为0和0.15%，持续10天），并通过吸入接触EDC（浓度分别为0、153、304、455 ppm（体积/体积）；每周5天，每天7小时，共接触30天）。在接触30天时，对肾脏、肝脏、脾脏和睾丸以及连续的尿液样本进行检测，通过同步电感耦合等离子体原子发射光谱法测定元素含量。每种化合物单独或联合使用时，相对于对照组，均产生了与EDC剂量相关（相关系数r大于或等于0.8）的器官金属含量变化。单独使用EDC时，肝脏中P和Sr含量增加，脾脏中Fe、Mg和P含量降低。在接触DSF的动物中，EDC导致肝脏中Ca、Cu、Fe、Mn和S含量增加，K含量降低；睾丸中Ca、Cu、Fe、Mn、Mo、P和S含量增加，Zn含量降低；脾脏中Fe含量增加，K含量降低；肾脏中P含量增加。单独使用DSF时，肝脏中Cu含量增加，但睾丸和肾脏中Cu含量降低；肝脏和肾脏中Pb含量增加，肝脏、脾脏和肾脏中Zn含量增加；肝脏中Al和Si含量增加，脾脏中S含量增加，肾脏中K含量增加；肾脏中Mn和Na含量降低。出现组织病理学变化的器官（肝脏和睾丸）中，Ca、Cu、Fe、Mn和S含量均增加。尿液中的金属元素表现出初次接触时的“冲击”影响，即Na的初始排泄以及大多数其他元素的潴留。在稳态（大于12天）后，单独使用EDC导致Sr和Zn含量增加；对于EDC - DSF组，除了DSF单独作用引起的变化（S和Zn含量增加，Cu含量降低）外，EDC还导致Na含量降低。从金属对谷胱甘肽解毒途径的影响、尿液中游离二乙基二硫代氨基甲酸盐的浓度以及与骨骼的相互作用等角度对结果进行了解释。EDC、DSF和EDC - DSF的作用机制除了有机中间体、代谢产物和酶之外，还必须考虑微量元素。
