壬基酚在SD大鼠内分泌腺、胃、心脏、肝脏、肾脏和血清的分布与消除
Distribution and Elimination of Nonylphenol in Endocrine Glands, Stomach, Heart, Liver, Kidney and Serum of SD Rats
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摘要: 研究壬基酚经消化道摄入后在SD大鼠的内分泌腺、胃、心脏、肝脏、肾脏和血清中的分布与消除情况。取39只SD雄性大鼠随机分为13组（每组3只），除对照组（一次性给予同等剂量玉米油）外其余各组一次性灌胃400 mg·kg-1的壬基酚，在灌胃后的0.25、0.5、1、2、4、8、12、24、48、72、96和120 h腹腔注射戊巴比妥钠麻醉处死大鼠，取其内分泌腺（胸腺、甲状腺和肾上腺）、胃、肝脏、肾脏、心脏和血清，使用高效液相色谱法检测壬基酚的含量，并计算代谢动力学相关参数。代谢动力学参数包括二室模型分布相半衰期（t1/2α）、曲线下面积（AUC）、自中央室向外周室转运速率常数（K12）、自外周室向中央室转运速率常数（K21）、平均驻留时间（MRT0~t）、二室模型清除相半衰期（t1/2β）、中央室总体清除率（CL/F）、自中央室消除速率常数（K10）、吸收相半衰期（t1/2Ka）。壬基酚在大鼠各器官组织内的代谢除肝脏外均为二室模型。在内分泌腺中，胸腺内峰浓度最大，cmax=4.927 mg·L-1，曲线下面积最大，AUC0~∞=766.163 mg·L-1·h、平均驻留时间最长，MRT0~t=53.901 h；肾上腺组织中壬基酚二室模型清除相半衰期最长，t1/2β=1 306 826.882 h；甲状腺组织中壬基酚的t1/2Ka=1.375 h、K12=0.275 h-1、K21=0.165 h-1、MRT0~t=50.705 h；在实质性器官中，胃组织中壬基酚的达峰时间最早，Tmax=2 h，峰浓度最高，cmax=41.4 mg·L-1，曲线下面积最大，AUC0~∞=364.319 mg·L-1·h；心脏组织中壬基酚的T1/2Ka=2.013 h，CL/F=7.228 L·kg-1·h-1；肝脏组织中壬基酚的K10=0.21 h-1；肾脏组织中各代谢动力学参数数值与肝脏相似；血清中的各项代谢动力学参数数值均处于中等水平。壬基酚主要分布在胸腺组织和胃组织中，在胃组织中驻留时间短易被吸收，在胸腺组织中驻留时间长且浓度高。壬基酚在肝脏和肾脏中清除率高。Abstract: To study the distribution and elimination of nonylphenol (NP) in the endocrine glands, stomach, heart, liver, kidney and serum of SD rats which are exposed to NP by gavage. Thirty-nine SD male rats were randomly divided into 13 groups (n=3 per group). The rats were gavaged with NP in corn oil at dose level of 400 mg·kg-1 or corn oil alone (vehicle control, C) once. At 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96 and 120 h after the last gavage, rats from all treatment groups were euthanized under deep anesthesia by intraperitioneal injection of pentobarbital sodium, respectively. NP concentrations in endocrine glands (i.e., thymus, thyroid, adrenal glands), stomach, liver, kidney, heart and serum were detected using the high performance liquid chromatography (HPLC) technique. Metabolokinetic parameters, including the half-life of distribution of two-compartment model (t1/2α), the half-life of elimination of two-compartment model (t1/2β), area under curve (AUC), distribution rate constant from central compartment to peripheral compartment (K12), distribution rate constant from peripheral compartment to central compartment (K21), mean residence time (MRT0~t), apparent clearance (CL/F) and elimination rate constant from the central compartment (K10), absorption half-life (t1/2Ka) were assessed. The metabolism of NP in all organs and tissues of rats was corresponding to a two-compartment model rather than liver. In the endocrine glands, the maximum peak concentration (cmax) for NP in thymus was 4.927 mg·L-1. The biggest (AUC0~∞) was 766.163 mg·L-1·h, and the longest MRT0~t was 53.901 h. t1/2β for NP in adrenal gland was 1 306 826.882 h, which was longest. t1/2Ka, K12, K21 and MRT0~t for NP in thyroid were 1.375 h, 0.275 h-1, 0.165 h-1 and 50.705 h, respectively. The peak time (Tmax), cmax and the biggest (AUC0~∞) for NP in stomach were 2 h, 41.4 mg·L-1, 364.319 mg·L-1·h, respectively. t1/2Ka and CL/F for NP in heart were 2.013 h and 7.228 L·kg-1·h-1. K10 for NP in liver was 0.21 h-1. The values of metabolokinetic parameters for NP in kidney was similar to those of the liver. The values of metabolokinetic parameters for NP in serum was at an intermediate level. NP is mainly distributed in the thymus and stomach. NP is absorbed easily in stomach with short residence time, while NP concentration is high in thymus with long residence time. NP could be eliminated in the liver and kidney with high clearance.
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Key words:
- nonylphenol /
- SD rats /
- endocrine glands /
- internal organs /
- distribution and elimination
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曹卫鑫. 大鼠4-壬基酚低剂量长期经口暴露代谢动力学研究及雌性生殖毒性初探[D]. 南京:东南大学, 2018:1 Cao W X. Toxicokinetics and reproductive toxicity from low-dose long-term exposure to 4-nonylphenol in female rats[D]. Nanjing:Southeast University, 2018:1 (in Chinese)
王伟华, 柳春红, 孙远明, 等. 大鼠尿液中壬基酚的代谢轮廓[J]. 高等学校化学学报, 2011, 32(10):2280-2285 Wang W H, Liu C H, Sun Y M, et al. Metabolic profiles of nonylphenol in rat urine[J]. Chemical Journal of Chinese Universities, 2011, 32(10):2280-2285(in Chinese)
Geens T, Neels H, Covaci A. Distribution of bisphenol-A, triclosan and n-nonylphenol in human adipose tissue, liver and brain[J]. Chemosphere, 2012, 87(7):796-802 Arukwe A, Thibaut R, Ingebrigtsen K, et al. In vivo and in vitro metabolism and organ distribution of nonylphenol in Atlantic salmon (Salmo salar)[J]. Aquatic Toxicology, 2000, 49(4):289-304 曹向可, 钱庆增, 董静, 等. 壬基酚在雌性大鼠体内的分布与清除[J]. 现代预防医学, 2010, 37(23):4418-4419 , 4422 Cao X K, Qian Q Z, Dong J, et al. The distribution and clearance of nonylphenol in female rats[J]. Modern Preventive Medicine, 2010, 37(23):4418-4419, 4422(in Chinese)
Green T, Swain C, van Miller J P, et al. Absorption, bioavailability, and metabolism of para-nonylphenol in the rat[J]. Regulatory Toxicology and Pharmacology, 2003, 38(1):43-51 范奇元, 金泰廙, 丁训诚, 等. 消化道摄入壬基酚在大鼠体内的分布与清除[J]. 环境与职业医学, 2002, 19(4):228-230 Fan Q Y, Jin T Y, Ding X C, et al. The distribution and clearance of nonylphenol given by alimentary tract in rats[J]. Journal of Labour Medicine, 2002, 19(4):228-230(in Chinese)
闫鹏, 郑剑, 徐景野, 等. 壬基酚和辛基酚联合毒性的初步研究[J]. 中国预防医学杂志, 2007(5):644-645 黄韩冬, 宁伟伟, 张桃, 等. 结直肠癌患者血清壬基酚含量测定及临床意义[J]. 中华实验外科杂志, 2017, 34(9):1568-1569 Huang H D, Ning W W, Zhang T, et al. Concentration detection and clinical study of nonylphenol in serum of patients with colorectal cancer[J]. Chinese Journal of Experimental Surgery, 2017, 34(9):1568-1569(in Chinese)
熊友健, 胡榕, 涂琼, 等. 高效液相色谱-荧光检测法测定性早熟女童血浆中双酚A和4-壬基酚的含量[J]. 儿科药学杂志, 2020, 26(6):35-38 Xiong Y J, Hu R, Tu Q, et al. Determination of bisphenol A and 4-nonylphenol in plasma of girls with precocious puberty by high performance liquid chromatography-fluorescence detection[J]. Journal of Pediatric Pharmacy, 2020, 26(6):35-38(in Chinese)
王林. 环境浓度NP长期暴露对雄性大鼠甲状腺功能与增生性病变的影响及锌硒茶干预研究[D]. 遵义:遵义医科大学, 2020:8-10 Wang L. Effects of chronic exposure to NP at environmental concentration on thyroid function and thyroid hyperplasia disease in male rats and the interventional effects of zinc selenium tea[D]. Zunyi:Zunyi Medical University, 2020:8 -10(in Chinese)
赵猛, 邸倩南, 刘腾, 等. UPLC-MS/MS法研究雌性大鼠低剂量4-壬基酚暴露的代谢动力学[J]. 食品工业科技, 2019, 40(18):224-228 Zhao M, Di Q N, Liu T, et al. Metabolic kinetics of low dose 4-nonylphenol exposure in female rats by ultra-high performance liquid chromatography-tandem mass spectrometry[J]. Science and Technology of Food Industry, 2019, 40(18):224-228(in Chinese)
Jeong S H, Jang J H, Cho H Y, et al. Gender differences in pharmacokinetics and tissue distribution of 4-n-nonylphenol in rats[J]. Archives of Toxicology, 2019, 93(11):3121-3139 Liu T, Cao W X, Di Q N, et al. Evaluation of toxicokinetics of nonylphenol in the adult female Sprague-Dawley rats using a physiologically based toxicokinetic model[J]. Regulatory Toxicology and Pharmacology, 2019, 105:42-50 -
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