Synergism in immunotoxicological effects due to repeated combined administration of arsenic and lead in mice
Synergism in immunotoxicological effects due to repeated combined administration of arsenic and lead in mice
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DOI：
10.1016/j.intimp.2005.09.011
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发表时间：
2006-03-01
影响因子：
5.6
通讯作者：
Sengupta, M
中科院分区：
文献类型：
--
作者：
Bishayi, B;Sengupta, M
砷和铅被认为是潜在的人类危害，因为它们会导致肿瘤；越来越多的流行病学证据表明，重金属接触与健康风险之间存在联系。由于单一给药金属的健康风险已得到证实，在本研究中，我们确定同时重复多金属（砷+铅）暴露是否会影响同时暴露于（体内）醋酸铅（10毫克/千克体重）和亚砷酸钠（0.5毫克/千克体重）的小鼠的免疫毒性发展。我们报道，体内多金属暴露会改变细胞形态，抑制细胞粘附、一氧化氮释放、细胞内杀伤能力、趋化迁移、髓过氧化物酶释放、血液和脾脏细菌清除，并增加DNA断裂。在对照组和多金属处理组感染（金黄色葡萄球菌MC524）后0、24、48和72 h血液和脾脏中的细菌密度测量中，多金属暴露组的细菌负荷表现为血液和脾脏的清除延迟。我们还发现，体内暴露于多金属导致细胞粘附减少，在570 nm处的吸光度与对照组相比下降。多金属暴露导致巨噬细胞形态改变，因为与对照组相比，反复联合暴露于砷和铅中获得的变形细胞更多。一氧化氮在巨噬细胞中具有强大的杀微生物活性，在多金属暴露组中释放的量比对照组少。结果表明，在对照组巨噬细胞中，细菌活力随时间逐渐降低，而在多金属暴露小鼠巨噬细胞中，金黄色葡萄球菌活力逐渐升高。多金属暴露组脾巨噬细胞趋化迁移较对照组明显减少。同时暴露于砷和铅时，脾巨噬细胞的溶酶体酶释放减少，多金属组髓过氧化物酶释放较对照组明显减少。多金属暴露组脾巨噬细胞结构完整性降低，DNA片段率升高，提示脾巨噬细胞凋亡。多金属暴露组脾巨噬细胞胞内活菌量为89.16 +/- 3.54%，对照组为49.19 +/- 1.16%，而砷和铅暴露组的胞内活菌量分别为69.6 +/- 2.45%和71.71 +/- 1.89%。从观察到的结果中最值得注意的是，铅和砷作为多种金属一起施用比单独施用时产生更大的免疫毒性作用。同时暴露于铅和砷似乎是可加性的，这一点从绘制砷浓度与铅浓度的等温线进一步确定，在这种情况下，效应（在这种情况下，髓过氧化物酶释放）保持不变，一条显示协同作用的凸线被证明。本研究报告了同时暴露于砷和铅时免疫毒性的明确协同趋势，即与单独暴露于砷和铅时的影响相比，是一种多金属挑战。(c) 2005 Elsevier B.V.版权所有
Arsenic and lead are considered potent human hazards because of their neoplastic outcomes; increasing epidemiologic evidence indicates a link between heavy metal exposure and health risk. Since health risks of singly administered metals are well-established, in the present study we determined whether simultaneous repeated multimetal (arsenic+ lead) exposure influences the development of immunotoxicity in mice exposed (in vivo) to lead acetate (10 mg/kg b.w.) and sodium arsenite (0.5 mg/kg b.w.) simultaneously. We report that in vivo multimetal exposure alters cell morphology, inhibits cell adhesion, nitric oxide release, intracellular killing ability, chemotactic migration, myeloperoxidase release, bacterial clearance from blood and spleen and increases DNA fragmentation. On measuring bacterial density in blood and spleen after 0, 24, 48 and 72 h post infection (with Staphylococcus aureus MC524) in control and multimetal treated groups, bacterial load showed delayed clearance from blood and spleen in the multimetal exposed group. We also found that in vivo exposure to the multimetal caused a decrease in cell adhesion, indicated by a fall in absorbance at 570 nm with respect to control. Exposure to multimetal led to morphological changes in macrophages, since more deformed cells were obtained in repeated combined exposure to arsenic and lead compared to control. Nitric oxide, which has a potent microbicidal activity in macrophages, was found to be released in fewer amounts in the multimetal exposed group from that of control group. It was observed that the viability of bacteria gradually decreased in control macrophage with time, whereas, in macrophages of multimetal exposed mice, the viability of S. aureus gradually increased. Chemotactic migration of splenic macrophages significantly decreased in the multimetal exposed group from that of control. Lysosomal enzyme release from splenic macrophages decreased upon simultaneous exposure to arsenic and lead, as is evident from the decrease in myeloperoxidase release in multimetal group from that in control. That the structural integrity of splenic macrophages is decreased in the multimetal exposed group is also evident from the enhanced percentage of DNA fragmentation after multimetal exposure, suggesting apoptotic death of splenic macrophage. Intracellular viable bacteria in the splenic macrophage from multimetal exposed group was 89.16 +/- 3.54% while that from control group was 49.19 +/- 1.16%, whereas single metal exposed groups showed a bacterial viability of 69.6 +/- 2.45% and 71.71 +/- 1.89% in arsenic and lead treated groups respectively. What is essentially noteworthy from the observed results is that lead and arsenic causes a greater immunotoxic effect when administered together as multimetal than when singly administered.Simultaneous exposure to lead and arsenic appears to be additive as is further established from the isobologram constructed by plotting the concentration of arsenic against the concentration of lead at which effect (in this case myeloperoxidase release) remained constant, a convex line showing synergism was demonstrated. The present study reports a definite synergistic trend of immunotoxicity during simultaneous exposure to arsenic and lead, that is, a multimetal challenge, as compared to the effects of independent exposure to them. (c) 2005 Elsevier B.V. All rights reserved.