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顺铂处理的足细胞中,凋亡诱导因子、蛋白表达及凋亡随谷氨酰胺的变化

Apoptosis-Inducing Factor, Protein Expression, and Apoptosis Changes with Glutamine in Podocytes Cells Exposed with Cisplatin.

作者信息

Susilo Imam, Maulida Himmayatussorofil, Alimsardjono Lindawati, Fauziah Dyah, Pertiwi Herinda

机构信息

Department of Pathological Anatomy, Universitas Airlangga, Jalan Mayjen Prof. Dr. Moestopo 47, Surabaya, Indonesia.

Medicine Undergraduate Program, Universitas Airlangga, Jalan Mayjen Prof. Dr. Moestopo 47, Surabaya, Indonesia.

出版信息

Vet Med Int. 2021 Apr 21;2021:5599452. doi: 10.1155/2021/5599452. eCollection 2021.

Abstract

Cisplatin is a well-known chemotherapeutic drug. It is one of the most effective anticancer agents and is widely used for the treatment of several types of tumors. However, side effects in normal tissues and organs, such as nephrotoxicity that induces apoptosis in epithelial cells in the kidney, limit the use of cisplatin. Glutamine is a substrate for the synthesis of glutathione as an antioxidant and promotes HSP70 release, protecting cells from apoptosis induced by different stimuli. In the present study, we investigated the protective effect of glutamine on cisplatin nephrotoxicity in the kidney. Mice were divided into three groups such as a group of control (P0), a group of intraperitoneal injection of a single dose cisplatin 20 mg/kg BW at 7th day (P1), and a group of intravenous glutamine injection 100 mg/kg BW at days 1-7 and given an intraperitoneal injection of single dose cisplatin 20 mg/kg BW at 7th day (P2). Measurement of AIF expression and apoptotic cells was carried out by immunohistochemical methods. The number of AIF expressions and apoptotic cells is expressed in the Allred score. AIF expression result is as follows: P0: 3.29 ± 0.79, P1: 5.32 ± 0.68, and P2: 4.49 ± 0.47. Apoptosis result is as follows: P0: 3.04 ± 0.70, P1: 5.26 ± 0.53, and P2: 4.44 ± 0.41. There is a decreased expression of AIF on intravenous glutamine administration, followed by a decrease in apoptosis in the podocyte. In conclusion, glutamine administration might represent the treatment of nephrotoxic-induced cisplatin.

摘要

顺铂是一种著名的化疗药物。它是最有效的抗癌药物之一,广泛用于治疗多种类型的肿瘤。然而,顺铂对正常组织和器官的副作用,如导致肾上皮细胞凋亡的肾毒性,限制了其应用。谷氨酰胺是合成作为抗氧化剂的谷胱甘肽的底物,并促进热休克蛋白70(HSP70)释放,保护细胞免受不同刺激诱导的凋亡。在本研究中,我们调查了谷氨酰胺对顺铂所致肾毒性的保护作用。将小鼠分为三组,即对照组(P0)、在第7天腹腔注射单剂量20 mg/kg体重顺铂的组(P1)、在第1 - 7天静脉注射100 mg/kg体重谷氨酰胺并在第7天腹腔注射单剂量20 mg/kg体重顺铂的组(P2)。通过免疫组织化学方法检测凋亡诱导因子(AIF)表达和凋亡细胞。AIF表达和凋亡细胞数量以奥尔雷德评分表示。AIF表达结果如下:P0:3.29±0.79,P1:5.32±0.68,P2:4.49±0.47。凋亡结果如下:P0:3.04±0.70,P1:5.26±0.53,P2:4.44±0.41。静脉注射谷氨酰胺后AIF表达降低,随后足细胞凋亡减少。总之,给予谷氨酰胺可能是治疗顺铂所致肾毒性的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2161/8081609/104ba206a092/VMI2021-5599452.001.jpg

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