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壳聚糖纳米粒包封姜黄素:一种治疗砷毒性的新策略。

Curcumin encapsulated in chitosan nanoparticles: a novel strategy for the treatment of arsenic toxicity.

机构信息

Division of Pharmacology and Toxicology, Defense Research and Development Establishment, Gwalior 474 002, India.

出版信息

Chem Biol Interact. 2012 Jul 30;199(1):49-61. doi: 10.1016/j.cbi.2012.05.011. Epub 2012 Jun 13.

Abstract

Water-soluble nanoparticles of curcumin were synthesized, characterized and applied as a stable detoxifying agent for arsenic poisoning. Chitosan nanoparticles of less than 50 nm in diameter containing curcumin were prepared. The particles were characterized by TEM, DLS and FT-IR. The therapeutic efficacy of the encapsulated curcumin nanoparticles (ECNPs) against arsenic-induced toxicity in rats was investigated. Sodium arsenite (2mg/kg) and ECNPs (1.5 or 15 mg/kg) were orally administered to male Wistar rats for 4 weeks to evaluate the therapeutic potential of ECNPs in blood and soft tissues. Arsenic significantly decreased blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity, reduced glutathione (GSH) and increased blood reactive oxygen species (ROS). These changes were accompanied by increases in hepatic total ROS, oxidized glutathione, and thiobarbituric acid-reactive substance levels. By contrast, hepatic GSH, superoxide dismutase and catalase activities significantly decreased on arsenic exposure, indicative of oxidative stress. Brain biogenic amines (dopamine, norepinephrine and 5-hydroxytryptamine) levels also showed significant changes on arsenic exposure. Co-administration of ECNPs provided pronounced beneficial effects on the adverse changes in oxidative stress parameters induced by arsenic. The results indicate that ECNPs have better antioxidant and chelating potential (even at the lower dose of 1.5 mg/kg) compared to free curcumin at 15 mg/kg. The significant neurochemical and immunohistochemical protection afforded by ECNPs indicates their neuroprotective efficacy. The formulation provides a novel therapeutic regime for preventing arsenic toxicity.

摘要

合成了载姜黄素的水溶性纳米粒子,并对其进行了特性分析,将其作为一种稳定的砷中毒解毒剂。制备了载姜黄素的壳聚糖纳米粒子,粒径小于 50nm。采用 TEM、DLS 和 FT-IR 对粒子进行了表征。研究了包封姜黄素纳米粒子(ECNPs)对大鼠砷中毒的治疗效果。向雄性 Wistar 大鼠口服亚砷酸钠(2mg/kg)和 ECNPs(1.5 或 15mg/kg)4 周,以评估 ECNPs 在血液和软组织中的治疗潜力。砷显著降低了血液 δ-氨基酮戊酸脱水酶(δ-ALAD)活性、还原型谷胱甘肽(GSH),并增加了血液活性氧(ROS)。这些变化伴随着肝总 ROS、氧化型谷胱甘肽和硫代巴比妥酸反应物质水平的增加。相反,肝 GSH、超氧化物歧化酶和过氧化氢酶活性在砷暴露后显著降低,表明存在氧化应激。脑生物胺(多巴胺、去甲肾上腺素和 5-羟色胺)水平在砷暴露后也发生了显著变化。ECNPs 的共给药对砷诱导的氧化应激参数的不良变化提供了显著的有益影响。结果表明,与 15mg/kg 的游离姜黄素相比,ECNPs 具有更好的抗氧化和螯合潜力(即使在较低的 1.5mg/kg 剂量下)。ECNPs 提供的显著神经化学和免疫组织化学保护表明其具有神经保护作用。该制剂为预防砷毒性提供了一种新的治疗方案。

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