摘要
目的探讨锌对幼龄大鼠砷暴露后不同价态砷的体内药动学及组织分布,为幼龄儿童砷暴露风险控制及防护提供科学数据的支撑。方法24只3周龄SD大鼠随机分为三氧化二砷(arsenic trioxide,ATO)单次组、锌预给药组和ATO+锌共处理组等3组,按组干预,采用高效液相色谱-电感耦合等离子体质谱技术(HPLC-ICP/MS)测定各组不同时间点的血浆砷形态及浓度,测定各组脏器砷蓄积。采用DAS 2.0软件分析获取不同砷形态的药动学参数。结果血浆砷代谢动力学显示,给药15 min,各组血浆中三价砷(As^(Ⅲ))最大浓度排序为ATO单次组>锌预给药组>ATO+锌共处理组,其中锌预给药组给药2 h后逐渐趋于低水平,早于ATO组的下降时间。ρ_(max)、t_(max)和t_(1/2)参数提示补充锌后加快了As^(Ⅲ)向五价砷(As^(Ⅴ))氧化的速度;一级甲基化指数(primary methylation index,SMI)、单甲基砷比例(the proportion of monomethylarsonic acid,MMA%)、二甲基砷比例(the proportion of dimethylarsinic acid,DMA%)升高,无机砷比例(the proportion of inorganic arsenic,iAs%)显著降低则提示甲基化能力增强。组织分布测定结果表明,补充锌可降低全脑、肺脏、肾脏、睾丸、肝脏和脾脏组织的总砷(total arsenic,TAs)浓度,其中全脑、肺脏、肾脏、睾丸组织较ATO单次组显著降低(P<0.05)。结论锌能通过提高As^(Ⅲ)、As^(Ⅴ)在血浆及脏器中代谢速度,增强甲基化效率,有效减少砷代谢物在体内的生物蓄积,以达到减轻砷毒性目的。
OBJECTIVE To explore the in vivo pharmacokinetics and tissue distribution of zinc in different valence forms of arsenic in young rats after arsenic exposure in young rats,thus to provide scientific data to support the risk control and protection of arsenic exposure in young children.METHODS Twenty-four 3-week-old SD rats were randomly divided into three groups:a single-dose arsenic trioxide(ATO)group,a zinc pre-administration group,and an ATO+zinc co-treatment group.The rats were treated accordingly to their group assignments.High-performance liquid chromatography-inductively coupled plasma mass spectrometry(HPLC-ICP/MS)was used to measure the arsenic species and concentrations in plasma at different time points,as well as the arsenic accumulation in various organs.Pharmacokinetic parameters for different arsenic species were analyzed using DAS 2.0 software.RESULTS The pharmacokinetics of arsenic in plasma showed that 15 min after administration,the maximum concentration of trivalent arsenic(As^(Ⅲ))in plasma was highest in the ATO single-dose group,followed by the zinc pre-administration group,and then the ATO+zinc co-treatment group.The zinc pre-administration group reached lower levels 2 h after administration,earlier than the ATO group.Parameters such asρ_(max),t_(max),and t_(1/2)indicated that zinc supplementation accelerated the oxidation of As^(Ⅲ)to pentavalent arsenic(As^(Ⅴ)).The increase in the primary methylation index(SMI),the proportion of monomethylarsonic acid(MMA%),and the proportion of dimethylarsinic acid(DMA%),along with a significant decrease in the proportion of inorganic arsenic(iAs%),suggested enhanced methylation capacity.Tissue distribution measurements showed that zinc supplementation reduced the total arsenic(TAs)concentration in the brain,lungs,kidneys,testes,liver,and spleen.Notably,the brain,lungs,kidneys,and testes showed significantly lower TAs concentrations compared with the ATO single-dose group(P<0.05).CONCLUSION Zinc can effectively reduce the bioaccumulation of arsenic metabolites in the body by increasing the metabolic rates of As^(Ⅲ)and As^(Ⅴ)in plasma and organs,enhancing the methylation efficiency to achieve the protection against arsenic toxicity.
作者
李妙琳
徐优慧
黄凯锋
曾慧敏
周翔
史云霞
徐玥雯
杨建豪
江珍红
徐焕华
刘潜
LI Miaolin;XU Youhui;HUANG Kaifeng;ZENG Huimin;ZHOU Xiang;SHI Yunxia;XU Yuewen;YANG Jianhao;JIANG Zhenhong;XU Huanhua;LIU Qian(Discipline of Chinese and Western Integrative Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Institute of Integrative Chinese and Western Medicine Children′s Health and College of Traditional Chinese Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China;National Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Jiangxi Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Nanchang 330006,China)
出处
《中国药学杂志》
北大核心
2025年第10期1050-1056,共7页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(82304857、82460814)
江西省自然科学基金项目资助(20224BAB216105、20232BAB206167、20242BAB25577)。
作者简介
李妙琳,女,硕士研究生,研究方向:中西医临床;通信作者:徐焕华,男,副教授,研究方向:中药药理与毒理,Tel:(0791)87114554;通信作者:刘潜,男,教授,研究方向:中西医儿童疾病防治,Tel:(0791)87114554。
