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姜黄素和香叶醇通过下调 p38MAPK/STAT-1 通路和氧化应激缓解顺铂诱导的大鼠神经毒性。

Thymoquinone and geraniol alleviate cisplatin-induced neurotoxicity in rats through downregulating the p38 MAPK/STAT-1 pathway and oxidative stress.

机构信息

Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt.

Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.

出版信息

Life Sci. 2019 Jul 1;228:145-151. doi: 10.1016/j.lfs.2019.04.065. Epub 2019 Apr 30.

DOI:10.1016/j.lfs.2019.04.065
PMID:31047895
Abstract

AIMS

Cisplatin (CP) is a widely used broad-spectrum antineoplastic agent used to treat a variety of human malignancies. Neurotoxicity is clinically evident in patients who have undergone a full course of chemotherapy. The aim of this study was to investigate the possible protective effects of thymoquinone (TQ) and geraniol (Ger) against CP-induced neurotoxicity in rats.

MAIN METHODS

Forty male Wistar albino rats were allocated into four groups as follows: normal control, CP-induced neurotoxicity, CP + TQ and CP + Ger.

KEY FINDINGS

Our results demonstrated that simultaneous treatment with either TQ or Ger and CP significantly abrogated oxidative stress and downregulated the apoptotic markers p38 mitogen-activated protein kinase (MAPK), STAT-1, p53, p21 and MMP9; FMO3, however, was insignificantly decreased. In addition to the biochemical results, we assessed the histopathological findings, which confirmed the protective effect of TQ and Ger against the brain damage induced by CP.

SIGNIFICANCE

The results of the present study indicate that simultaneous treatment with either TQ or Ger as natural antioxidants can provide protection against cisplatin-induced neurotoxicity in rats by attenuating oxidative stress and cell apoptosis.

摘要

目的

顺铂(CP)是一种广泛应用的广谱抗肿瘤药物,用于治疗多种人类恶性肿瘤。神经毒性在接受完整化疗疗程的患者中表现为临床症状。本研究旨在探讨姜黄素(TQ)和香叶醇(Ger)对 CP 诱导的大鼠神经毒性的可能保护作用。

主要方法

将 40 只雄性 Wistar 白化大鼠分为四组:正常对照组、CP 诱导的神经毒性组、CP+TQ 组和 CP+Ger 组。

主要发现

我们的结果表明,TQ 或 Ger 与 CP 同时治疗可显著减轻氧化应激,并下调凋亡标志物 p38 丝裂原活化蛋白激酶(MAPK)、STAT-1、p53、p21 和 MMP9;然而,FMO3 降低不明显。除了生化结果外,我们还评估了组织病理学发现,证实了 TQ 和 Ger 对 CP 诱导的脑损伤的保护作用。

意义

本研究结果表明,TQ 或 Ger 作为天然抗氧化剂同时治疗可通过减轻氧化应激和细胞凋亡提供对 CP 诱导的大鼠神经毒性的保护作用。

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