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评估香菇多糖在顺铂诱导的氧化肾损伤中的作用。

Evaluating the role of polysaccharide extracted from Pleurotus columbinus on cisplatin-induced oxidative renal injury.

机构信息

Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Dokki, Cairo, Egypt.

Department of Radioisotopes, Nuclear Research Centre, Egyptian Atomic Energy Authority, Cairo, Egypt.

出版信息

Sci Rep. 2023 Jan 16;13(1):835. doi: 10.1038/s41598-022-27081-2.

Abstract

This research aimed to examine the antioxidant polysaccharide activity (PsPc-3) derived from Pleurotus columbinus (P. columbinus) on oxidative renal injury (ORI) induced by cisplatin (CP). The principal components of crude polysaccharide were assessed. We studied the preventive impact of polysaccharide on cisplatin-induced renal damage in this study. For 21 days, we employed the CP-induced ORI rat model and divided the rats into four groups: control, CP alone, polysaccharide post CP (100 mg/kg) orally, and CP + polysaccharide (pre and post). The chemical characterization of the polysaccharide fraction PsPc-3 stated that protein was not present. PsPc-3 contained 7.2% uronic acid as assessed as 0% sulfate. PsPc-3 hydrolysate structured of Galacturonic:Glucose:Xylose and their molar proportions were 1:4:5, respectively. The average molecular weight (Mw) and molecular mass (Mn) per molecule of PsPc-3 were 5.49 × 10 g/mol and Mn of 4.95 × 10 g/mol respectively. DPPH radical scavenging activity was demonstrated by the polysaccharide of 65.21-95.51% at 10 mg/ml with IC50 less than 10 mg/ml. CP increased serum urea to 92.0 mg/dl and creatinine up to 1.0 mg/dl, with a concurrent decrease in the levels of total protein to 4.0 mg/dl. Besides, Also, CP-induced ORI raised levels of malondialdehyde (MDA), alkaline phosphatase (ALP), and renal hormones (renin and aldosterone), with a decline in antioxidants compared to control rats. In addition, in the presence of CP, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels increased. PsPc-3 decreased these changes dramatically. PsPc-3 improves pathological renal damage caused by CP and decreases tubular apoptosis measured by DNA ladder formation and cleaved caspase- 3. These findings showed that PsPc-3 isolated from P. columbinus protects and inhibits tubular apoptosis in cisplatin-induced ORI. Furthermore, PsPc-3 has no influence on the anticancer efficacy of CP in rats. Thus, PsPc-3 derived from P. columbinus might provide a novel therapy method for cisplatin-induced nephrotoxicity.

摘要

本研究旨在探讨来源于香菇(Pleurotus columbinus)的抗氧化多糖(PsPc-3)对顺铂(CP)诱导的氧化性肾损伤(ORI)的活性。评估了粗多糖的主要成分。我们在这项研究中研究了多糖对 CP 诱导的肾损伤的预防作用。在 21 天的时间里,我们使用 CP 诱导的 ORI 大鼠模型,将大鼠分为四组:对照组、CP 组、CP 后多糖(100mg/kg)口服组和 CP+多糖(预和后)组。多糖部分 PsPc-3 的化学特征表明不存在蛋白质。PsPc-3 含有 7.2%的糖醛酸,硫酸含量为 0%。PsPc-3 水解产物由半乳糖醛酸:葡萄糖:木糖组成,摩尔比例分别为 1:4:5。PsPc-3 的平均分子量(Mw)和每个分子的分子量(Mn)分别为 5.49×10 g/mol 和 4.95×10 g/mol。多糖的 DPPH 自由基清除活性在 10 mg/ml 时为 65.21-95.51%,IC50 小于 10 mg/ml。CP 将血清尿素提高到 92.0 mg/dl,肌酐提高到 1.0 mg/dl,同时总蛋白水平降低到 4.0 mg/dl。此外,CP 诱导的 ORI 还会导致丙二醛(MDA)、碱性磷酸酶(ALP)和肾激素(肾素和醛固酮)水平升高,与对照组大鼠相比,抗氧化剂水平下降。此外,在 CP 的存在下,白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平升高。PsPc-3 显著降低了这些变化。PsPc-3 可改善 CP 引起的病理性肾损伤,并通过 DNA 梯形成和半胱天冬酶-3 的裂解来减少管状细胞凋亡。这些发现表明,从香菇中分离出的 PsPc-3 可保护并抑制顺铂诱导的 ORI 中的管状细胞凋亡。此外,PsPc-3 对 CP 在大鼠中的抗癌功效没有影响。因此,来源于香菇的 PsPc-3 可能为顺铂诱导的肾毒性提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6174/9842759/02f8bb2f4194/41598_2022_27081_Fig1_HTML.jpg

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