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脂质体包裹的内消旋-2,3-二巯基琥珀酸对通过饮水接触铅的小鼠的影响。

Effect of liposome-encapsulated meso-2,3-dimercaptosuccinic acid on mice exposed to lead through drinking water.

作者信息

Misra M, Behari J R

机构信息

Industrial Toxicology Research Centre, Lucknow.

出版信息

Boll Chim Farm. 1997 Nov;136(10):611-4.

PMID:9528168
Abstract

Liposomes are the potent carriers of therapeutic drugs for their targeted delivery to the intracellular sites specially when the drug is hydrophilic in nature and is unable to cross the cell membrane. Lead, a major source of environmental pollution, is accumulated in the body system of both animals and humans through reticuloendothelial system, the site where liposomes also get engulfed upon their entry into the body. In view of these considerations, meso-2,3 dimercaptosuccinic acid (DMSA), a potent chelating drug used in heavy metals intoxication, specially lead, was encapsulated in small unilamellar liposomes composed of phosphatidyl-choline and cholesterol (1:1) and used to evaluate its efficacy in lead intoxication. DMSA either in free form or encapsulated in liposomes was administered intravenously (2,62 mumoles/kg, three injections at a gap of 48 hours each, total 7.85 mumoles/kg) to mice which were pre-fed with lead in drinking water (500 micrograms/ml) for one month. It was found that only DMSA encapsulated in liposomes was significantly effective in reducing the level of lead in liver, kidneys and spleen at the dose administered. DMSA either in free form or encapsulated in liposomes also restored the inhibition in blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. The results suggest that liposome encapsulated DMSA may be preferred over free DMSA for reducing the body burden of lead.

摘要

脂质体是治疗药物的有效载体,可将药物靶向递送至细胞内位点,特别是当药物具有亲水性且无法穿过细胞膜时。铅是环境污染的主要来源,它通过网状内皮系统在动物和人类的身体系统中蓄积,而脂质体进入人体后也会被该系统吞噬。鉴于这些考虑因素,将用于重金属中毒(特别是铅中毒)的强效螯合药物中-2,3-二巯基琥珀酸(DMSA)包裹在由磷脂酰胆碱和胆固醇(1:1)组成的小单层脂质体中,并用于评估其在铅中毒治疗中的疗效。将游离形式或包裹在脂质体中的DMSA静脉注射(2.62微摩尔/千克,每隔48小时注射一次,共三次,总量7.85微摩尔/千克)给预先在饮用水中添加铅(500微克/毫升)一个月的小鼠。结果发现,在所给药剂量下,只有包裹在脂质体中的DMSA能显著有效降低肝脏、肾脏和脾脏中的铅含量。游离形式或包裹在脂质体中的DMSA还能恢复血液中δ-氨基乙酰丙酸脱水酶(δ-ALAD)活性的抑制。结果表明,与游离DMSA相比,脂质体包裹的DMSA可能更有利于减轻体内铅负荷。

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