Kraus A L, Bernstein I A
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109-2029.
J Toxicol Environ Health. 1989;26(2):157-74. doi: 10.1080/15287398909531242.
A previous study established that 2,2',4,4',5,5'-hexabromobiphenyl (HBB) entered 3T3L1 adipocytes in culture by passive diffusion from the surrounding medium. The extent to which HBB accumulated within the cell was mediated by the level of triglyceride in the cell. The present study was concerned with the conditions that would facilitate HBB removal from adipocytes as part of a continuing effort to establish an effective and safe technology for reducing body burdens of lipophilic xenobiotics. Addition of human lipoprotein to the culture medium increased HBB removal from preloaded adipocytes 18 to 80 times more than did the addition of other blood proteins. Lipoproteins also decreased equilibrium deposition of HBB in the cells. The order of effect was low-density lipoprotein (LDL) much greater than high-density lipoproteins (HLD) greater than very-low-density lipoproteins (VLDL). These results are consistent with the hypothesis that lipoproteins act as a depot by binding HBB to immobilize the xenobiotic in the medium. The rate of removal of HBB was correlated with concentrations of lipoprotein cholesterol, cholesterol ester, and phospholipid in the culture medium (r greater than .95). Total lipoprotein fractions from individuals with high levels of serum cholesterol significantly increased HBB removal from preloaded adipocytes when compared with lipoproteins from normal human serum. Decreased removal was observed with lipoproteins from individuals with low serum cholesterol or triglyceride. These results suggest that cholesterol and/or cholesterol esters in the blood play an important role in both delivery and removal of HBB from the adipose tissue. Evidence has been presented that supports the hypothesis that HBB moves freely across the adipocyte membrane and is sequestered in either the cell or pseudoblood according to its relative solubility in these compartments.
先前的一项研究证实,2,2',4,4',5,5'-六溴联苯(HBB)通过从周围培养基的被动扩散进入培养的3T3L1脂肪细胞。HBB在细胞内的积累程度由细胞内甘油三酯水平介导。本研究关注的是有助于从脂肪细胞中去除HBB的条件,这是建立一种有效且安全的技术以减轻亲脂性外源性物质身体负担的持续努力的一部分。向培养基中添加人脂蛋白比添加其他血液蛋白能使预先加载的脂肪细胞中HBB的去除增加18至80倍。脂蛋白还降低了HBB在细胞中的平衡沉积。作用顺序为低密度脂蛋白(LDL)远大于高密度脂蛋白(HDL)大于极低密度脂蛋白(VLDL)。这些结果与脂蛋白通过结合HBB将外源性物质固定在培养基中而作为储存库的假设一致。HBB的去除速率与培养基中脂蛋白胆固醇、胆固醇酯和磷脂的浓度相关(r大于0.95)。与正常人血清中的脂蛋白相比,血清胆固醇水平高的个体的总脂蛋白组分显著增加了预先加载的脂肪细胞中HBB的去除。血清胆固醇或甘油三酯水平低的个体的脂蛋白观察到去除减少。这些结果表明血液中的胆固醇和/或胆固醇酯在HBB从脂肪组织的递送和去除中都起重要作用。已有证据支持HBB自由穿过脂肪细胞膜并根据其在这些隔室中的相对溶解度被隔离在细胞或假血液中的假设。