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展望褐藻糖胶通过内质网应激动态对奥沙利铂引起的雄性大鼠脾功能障碍的影响。

The prospective effect of fucoidan on splenic dysfunction caused by oxaliplatin in male rats through endoplasmic stress dynamics.

机构信息

Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt.

Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Sci Rep. 2022 Dec 22;12(1):22147. doi: 10.1038/s41598-022-25441-6.

Abstract

Fucoidans (FUCs) are highly sulfated polysaccharides demonstrating multiple actions in different systems. Oxaliplatin (OXA) is a platinum-containing chemotherapeutic agent with several side effects that restrict its usage. The current study aimed to determine the potential effect of FUC in male rats with splenic dysfunction induced by OXA. Eighty adult male rats aged (8-9 weeks) weighing (190-230 g) were divided into four groups: (Group I: the control group): Rats were administrated normal saline; (Group II: controls treated by FUC): Rats were treated with FUC; (Group III: Splenic dysfunction group): Rats were treated with 8 mg/kg OXA. (IV: Splenic dysfunction treated by FUC): Rats were treated by OXA as Group III, then fucoidan was given. At the end of the experiment, blood was collected to determine red blood cells and white blood cells. Splenic tissues were divided into one part for biochemical assays, oxidative stress markers as MDA and catalase, inflammatory markers (TNF-alpha, IL6), and apoptotic markers (caspase 3) and gene expression of Nrf2, Mapk1 gene expression, and endoplasmic stress parameters and the other part was used for immunohistochemical and histopathological analysis. Compared to the OXA-induced splenic dysfunction group, FUC significantly decreased high levels of MDA, TNF- alpha, IL6, caspase-3, Mapk1, endoplasmic stress induced by OXA, and increased the level of catalase and Nrf2. Fucoidan has corrected the histopathological and immunohistochemical changes compared to the OXA-induced splenic dysfunction group. In conclusion, our findings suggest that fucoidan has a significant role in the treatment of splenic dysfunction induced by OXA.

摘要

岩藻聚糖(FUCs)是一种高度硫酸化的多糖,在不同的系统中具有多种作用。奥沙利铂(OXA)是一种含铂的化疗药物,具有多种副作用,限制了其使用。本研究旨在确定 FUC 在 OXA 诱导的脾功能障碍雄性大鼠中的潜在作用。

将 80 只成年雄性大鼠(8-9 周龄)分为四组:(I 组:对照组):大鼠给予生理盐水;(II 组:对照组给予 FUC):大鼠给予 FUC;(III 组:脾功能障碍组):大鼠给予 8mg/kg OXA。(IV 组:脾功能障碍治疗组):大鼠如 III 组给予 OXA,然后给予 FUC。

实验结束时,采集血液以确定红细胞和白细胞。将脾组织分为两部分,一部分用于生化测定、氧化应激标志物 MDA 和过氧化氢酶,炎症标志物(TNF-α、IL6)和凋亡标志物(caspase 3)以及 Nrf2、Mapk1 基因表达,内质网应激参数,另一部分用于免疫组织化学和组织病理学分析。

与 OXA 诱导的脾功能障碍组相比,FUC 显著降低了 MDA、TNF-α、IL6、caspase-3、Mapk1、OXA 诱导的内质网应激水平,并增加了过氧化氢酶和 Nrf2 的水平。与 OXA 诱导的脾功能障碍组相比,FUC 纠正了组织病理学和免疫组织化学变化。

总之,我们的研究结果表明,FUC 在治疗 OXA 诱导的脾功能障碍方面具有重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cbc/9780252/abb228b649af/41598_2022_25441_Fig1_HTML.jpg

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