氧化纳米颗粒对度和时间的反应的分离性毒性影响 in vivo
Nouf M Alyami1, Ghufran A Almuhaini2, Hussah Alobaid2
1Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. nalyami@ksu.edu.sa.
Scientific reports
|June 6, 2025
概括
兰氧化物纳米粒子 (La2O3 NPs) 在小鼠中引起和肝损伤,炎症和矿物质失衡与NP剂量和暴露时间有关. 较低剂量显示出更大的毒性,可能是由于纳米粒子特性.
科学领域:
- 纳米技术纳米技术
- 毒理学 毒理学 毒理学
- 环境健康 环境健康
背景情况:
- 兰氧化物纳米粒子 (La2O3NP) 具有独特的电子特性和越来越多的应用.
- 潜在的La2O3 NP暴露引起了人们对生物积累和代谢中断的担忧.
- 和肝毒性是与纳米粒子暴露相关的重大健康风险.
研究的目的:
- 为了研究La2O3NP对小鼠脏在腹腔内给药后的影响.
- 评估La2O3NP的剂量依赖和时间依赖的毒理作用.
- 为了识别和肝功能障碍和炎症的生物标志物.
主要方法:
- 在小鼠身上,La2O3 NPs被输入腹腔内,剂量为60,150和300mg/kg,持续14天和35天.
- 评估了SOD基因表达,GSH血水平和NOS2转录.
- 测量KIM-1,尿酸,尿素,ALP,ALT和AST水平,以表明器官功能障碍.
- 利用蛋白质阵列用于脏炎症标志物和ICP-MS用于矿物平衡分析.
主要成果:
- La2O3 NP剂量与SOD基因表达/GSH血水平之间的反相关性.
- 在NP剂量和NOS2转录之间存在正相关性,表明剂量依赖性炎症.
- 和肝功能障碍标志物的显著增加 (KIM-1,尿酸,尿素,ALP,ALT,AST),特别是在较低的NP剂量下.
- 矿物质平衡的破坏,特别是Ca2+的损失,以及脏炎症标志物的增加.
结论:
- 在小鼠中,La2O3 NPs诱导和肝功能障碍和炎症.
- 毒性与破坏矿物平衡 (Ca2+损失) 和潜在的La3+离子释放有关.
- 较低的NP度可能表现出更高的毒性,这是由于细胞透的增加和聚合的减少.
相关概念视频
Time Course of Drug Effect
2.2K
The progression of a drug's impact can be analyzed by examining both the concentration-time course and the effect-time course. The concentration-time course is determined by the drug's half-life and is influenced by factors such as its pharmacokinetics, including absorption, distribution, metabolism, and elimination. The effect of the drug is often related to its concentration in the plasma and is calculated using the maximum drug effect and the plasma concentration that generates 50...
2.2K
Drug Concentration Versus Time Correlation
1.3K
The plasma drug concentration-time curve is a crucial tool in pharmacokinetics, representing the drug's concentration in plasma at different time intervals post-administration. This curve illustrates the drug's journey from absorption into the systemic circulation, distribution to body tissues, and eventual elimination through excretion or biotransformation.
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the...
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the...
1.3K
Nonlinear Pharmacokinetics: Overview
575
Nonlinear or dose-dependent pharmacokinetics is a phenomenon that occurs when the pharmacokinetic parameters of certain drugs deviate from linear pharmacokinetics at higher doses. These drugs do not follow the expected first-order kinetics, where the rate of drug elimination is directly proportional to the drug concentration. Instead, they exhibit a nonlinear relationship, which can be attributed to several factors.
Nonlinearity can arise due to the saturation of plasma protein-binding or...
Nonlinearity can arise due to the saturation of plasma protein-binding or...
575
Renal Failure: Dose Adjustments
167
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
167
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
314
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
314
Nonlinear Pharmacokinetics: Causes of Nonlinearity
355
Nonlinearity in drug pharmacokinetics is caused by various factors influencing how a drug is absorbed, distributed, metabolized, and excreted. Understanding these nonlinear processes is crucial for predicting drug behavior in the body and optimizing drug dosing regimens.
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...
355


