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N-(2-羟基苯基)乙酰胺及其金纳米缀合物对顺铂诱导的急性肾损伤的衰减作用在小鼠体内的研究。

Attenuation of cisplatin-induced acute kidney injury by N-(2-Hydroxyphenyl) acetamide and its gold conjugated nano-formulations in mice.

机构信息

Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan.

Department of Anatomy, Ziauddin University, Karachi, Pakistan.

出版信息

Pak J Pharm Sci. 2020 Mar;33(2(Supplementary)):787-793.

PMID:32863253
Abstract

The attenuation of cisplatin-induced acute kidney injury (AKI) in mice by N-(2-hydroxyphenyl) acetamide (NA-2) and NA-2-conjugated gold nanoparticles (NA2-AuNPs) was investigated. Male BALB/c mice (n = 54) were divided into nine groups having six animals in each group. Animals in groups 3-9 were pre-treated for 5 days with test compounds, whereas, animals in group 1 and 2 received normal saline. On day 4, animals in groups 2, 3, 4, 5, 6 and 9 were given single intra-peritoneal injection of CP at the dose of 5 mg/kg. After 72 hours of CP injection, all animals were sacrificed. Blood was collected for serum urea and creatinine estimation, and kidneys were harvested for histo-pathological examinations and qPCR studies for nuclear factor-κB p50, (NFκB) ; inducible nitric oxide synthase (iNOS); hemeoxygenase-1 (HO-1); and interleukin-6 (IL-6).NA-2 and NA2-AuNPs was observed to decrease the serum urea and creatinine levels. Both the test compounds reduced kidney injury damage score and improved histological architecture in the treated animals in dose dependent manner. Furthermore, the mRNA expressions of NFkB p50, iNOS and IL-6 genes were down-regulated, and HO-1 gene was up-regulated in the animals treated with the test compounds. It is concluded that NA-2 and NA2-AuNPs attenuates CP-induced AKI in mice models through anti-inflammatory and anti-oxidant mechanisms.

摘要

研究了 N-(2-羟基苯基)乙酰胺(NA-2)和 NA-2 缀合的金纳米粒子(NA2-AuNPs)对顺铂诱导的小鼠急性肾损伤(AKI)的衰减作用。将雄性 BALB/c 小鼠(n = 54)分为 9 组,每组 6 只动物。第 3-9 组动物用测试化合物预处理 5 天,而第 1 和 2 组动物给予生理盐水。第 4 天,第 2、3、4、5、6 和 9 组动物给予单次腹腔注射 CP 剂量为 5mg/kg。CP 注射后 72 小时,所有动物均被处死。采集血液用于血清尿素和肌酐测定,收集肾脏进行组织病理学检查和 qPCR 研究,用于核因子-κB p50(NFκB);诱导型一氧化氮合酶(iNOS);血红素加氧酶-1(HO-1);和白细胞介素-6(IL-6)。NA-2 和 NA2-AuNPs 观察到降低血清尿素和肌酐水平。两种测试化合物均降低了损伤评分,并改善了处理动物的组织学结构,呈剂量依赖性。此外,用测试化合物处理的动物中 NFkB p50、iNOS 和 IL-6 基因的 mRNA 表达下调,HO-1 基因上调。结论:NA-2 和 NA2-AuNPs 通过抗炎和抗氧化机制减轻 CP 诱导的 AKI 小鼠模型。

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