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一种针对疟疾感染中组织损伤的前瞻性策略:用壳聚糖-三聚磷酸酯偶联纳米氯喹在瑞士小鼠中进行研究。

A prospective strategy to restore the tissue damage in malaria infection: Approach with chitosan-trypolyphosphate conjugated nanochloroquine in Swiss mice.

机构信息

Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.

School of Chemical & Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu, India.

出版信息

Eur J Pharmacol. 2014 Aug 15;737:11-21. doi: 10.1016/j.ejphar.2014.04.030. Epub 2014 May 14.

Abstract

Accumulating evidence indicates that wide range of polymer based nanoconjugated drug have the ability to overcome the microbial infection. The present study was to evaluate the effects of nanoconjugated chloroquine (Nch) against Plasmodium berghei NK65 (P. berghei) infection on selective makers of oxidative damage, antioxidant status, pro-inflammatory and anti-inflammatory cytokines in liver and spleen. P. berghei infected Swiss mice were treated with Nch (250mg/kg bw for 15 days) compared with chloroquine. The stress markers, pro-inflammatory cytokines were increased significantly (P<0.05) and the anti-oxidant enzymes level, redox ratio (GSH/GSSG), anti-inflammatory markers were decreased significantly (P<0.05) in liver and spleen of infected mice compared with uninfected mice. Chloroquine and Nch effectively decreased the stress markers, pro-inflammatory cytokines, as well as, increased antioxidants level in liver and spleen of the infected mice. Moreover, the favorable effect Nch is better than the chloroquine defending the tissue damage during malarial infection. These findings suggested that the potential use and prospective role of Nch than only chloroquine against P. berghei induced pathology as well as oxidative damage in liver and spleen.

摘要

越来越多的证据表明,广泛的聚合物基纳米药物缀合物具有克服微生物感染的能力。本研究旨在评估纳米药物缀合物氯喹(Nch)对 Plasmodium berghei NK65(P. berghei)感染的影响,以及其对肝脏和脾脏氧化损伤、抗氧化状态、促炎和抗炎细胞因子的选择性标志物的影响。用 Nch(250mg/kg bw,15 天)处理感染 P. berghei 的瑞士小鼠,与氯喹进行比较。与未感染的小鼠相比,感染小鼠的应激标志物、促炎细胞因子显著增加(P<0.05),而肝脏和脾脏中的抗氧化酶水平、氧化还原比(GSH/GSSG)和抗炎标志物则显著降低(P<0.05)。氯喹和 Nch 能有效降低感染小鼠肝脏和脾脏中的应激标志物、促炎细胞因子,并增加抗氧化剂水平。此外,Nch 的这种有利作用优于氯喹,能在疟疾感染期间保护组织免受损伤。这些发现表明,Nch 具有潜在的应用和预期作用,不仅可以对抗 P. berghei 诱导的病理学,还可以对抗肝脏和脾脏中的氧化损伤。

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