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姜黄素通过 NF-κβ 和 HIF-1 机制保护小鼠免受 5-氟尿嘧啶诱导的黏膜炎。

Thymoquinone protects against 5-Fluorouracil-induced mucositis by NF-κβ and HIF-1 mechanisms in mice.

机构信息

Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran.

Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical, Babol University of Medical Sciences, Babol, Iran.

出版信息

J Biochem Mol Toxicol. 2023 Sep;37(9):e23405. doi: 10.1002/jbt.23405. Epub 2023 Jun 20.

DOI:10.1002/jbt.23405
PMID:37338137
Abstract

Mucositis is among the most common side effects of 5-Fluorouracil (5-FU) and other cancer therapeutic drugs. Thymoquinone (TQ), a bioactive constituent extracted from Nigella sativa, has antioxidant and anti-inflammatory properties and can modify acute gastrointestinal injury. To investigate the effects of TQ on mucositis induced by 5-FU, studied animals were divided into four groups: control, 5-FU unit dose (300 mg/kg) to cause oral and intestinal mucositis (OM and IM), TQ (2.5 mg/kg) and TQ (2.5 mg/kg) plus 5-FU. Due to The molecular mechanisms, it was confirmed that the expression of NF-κβ and HIF-1 increases in OM. The serum levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), as well as pathological parameters, were assessed. Based on our results, the nuclear factor-kappa β gene expression in the tongue was downregulated significantly in the 5-FU + TQ compared to the 5-FU. TQ treatment can diminish MDA, and a reduction in oxidative stress was shown. TQ could also reduce the severity of tissue destruction and damaging effects induced by 5-FU on the tongue and intestine. We also observed lower villus length and width in the intestine of the 5-FU group compared to the control group. According to our research's pathological, biochemical, and molecular results, treatment with TQ as an anti-inflammatory and antioxidant compound may be the potential to improve and treat 5-FU-induced OM and IM, and TQ could be used against cancer treatment drugs and exhibit fewer adverse effects.

摘要

黏膜炎是氟尿嘧啶(5-FU)和其他癌症治疗药物最常见的副作用之一。从黑种草中提取的活性成分百里醌(TQ)具有抗氧化和抗炎特性,可以改变急性胃肠道损伤。为了研究 TQ 对 5-FU 引起的黏膜炎的影响,研究动物被分为四组:对照组、给予 5-FU 单剂量(300mg/kg)引起口腔和肠道黏膜炎(OM 和 IM)、TQ(2.5mg/kg)和 TQ(2.5mg/kg)加 5-FU。由于分子机制,证实 OM 中 NF-κβ和 HIF-1 的表达增加。评估血清丙二醛(MDA)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的水平以及病理参数。根据我们的结果,与 5-FU 相比,5-FU+TQ 中舌核因子-κβ基因的表达明显下调。TQ 治疗可减少 MDA,并显示氧化应激减少。TQ 还可以减轻 5-FU 对舌和肠道组织的破坏和损伤作用。我们还观察到 5-FU 组肠绒毛长度和宽度比对照组小。根据我们研究的病理、生化和分子结果,作为一种抗炎和抗氧化化合物的 TQ 治疗可能有潜力改善和治疗 5-FU 引起的 OM 和 IM,并且 TQ 可用于对抗癌症治疗药物,表现出较少的不良反应。

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Antioxidants (Basel). 2024 Aug 25;13(9):1030. doi: 10.3390/antiox13091030.
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