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水飞蓟素,一种抗氧化黄酮类化合物,可保护肝脏免受抗癌药物紫杉醇的毒性影响。

Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel.

机构信息

Department of Histology and Embryology, Faculty of Medicine, Niğde Ömer Halisdemir University, Niğde, Turkey.

Department of Medical Biochemistry, Vocational School of Health Services, Adıyaman University, Adıyaman, Turkey.

出版信息

Tissue Cell. 2023 Aug;83:102158. doi: 10.1016/j.tice.2023.102158. Epub 2023 Jul 7.

Abstract

One of the biggest factors that negatively affect the cancer treatment plan is the toxic effects of chemotherapeutics on non-target cells and tissues. This information prompted us to investigate the protective effects of silymarin (SL), a hepatoprotective agent, against the hepatotoxic effects of the anticancer drug paclitaxel (PAC). Four groups were formed from 28 rats as control, PAC (2 mg/kg), SL (100 mg/kg) and PAC + SL (combination of PAC with SL). After completing the experimental procedures, the tissues collected after anesthesia were analyzed by Western blot, qRT-PCR, biochemical, stereological, immunohistochemical, and histopathological techniques. Administration of PAC significantly increased the expression of tumor necrosis factor-alpha (TNF-α), Bax, cytochrome-c (cyt-c), and active caspase-3, as well as malondialdehyde (MDA) levels in liver tissue and decreased glutathione (GSH) levels compared with the control group. PAC also resulted in a significant increase in serum triglyceride (TG), cholesterol (CH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the control group. Pathological changes such as microvesicular steatosis, the formation of Councilman bodies, an increase in total sinusoidal volume, and a decrease in the total number of hepatocytes were observed in the liver tissue of the PAC group. Almost all analysis results in the PAC + SL group were similar to those in the control group, and no significant pathological alterations were observed in this group. The data obtained show that SL protects the liver from the harmful effects of PAC, especially thanks to its TNF-α suppressor, anti-inflammatory, anti-apoptotic and antioxidant effects. Based on this result, in cases where PAC is used in cancer treatment, it can be recommended to be used together with SL to prevent harmful effects on healthy liver tissue and to continue treatment uninterruptedly and effectively.

摘要

影响癌症治疗计划的最大因素之一是化疗药物对非靶细胞和组织的毒性作用。这一信息促使我们研究水飞蓟素(SL),一种保肝剂,对抗癌药物紫杉醇(PAC)的肝毒性作用的保护作用。将 28 只大鼠分为四组,分别为对照组、PAC(2mg/kg)组、SL(100mg/kg)组和 PAC+SL(PAC 与 SL 联合组)。在完成实验程序后,用 Western blot、qRT-PCR、生化、立体学、免疫组织化学和组织病理学技术分析麻醉后收集的组织。与对照组相比,PAC 给药显著增加了肿瘤坏死因子-α(TNF-α)、Bax、细胞色素-c(cyt-c)和活性 caspase-3 的表达,以及肝组织中丙二醛(MDA)水平,并降低了谷胱甘肽(GSH)水平。PAC 还导致血清甘油三酯(TG)、胆固醇(CH)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平与对照组相比显著增加。与对照组相比,PAC 组肝组织中观察到微泡性脂肪变性、Councilman 体形成、总窦状间隙体积增加和肝细胞总数减少等病理变化。PAC+SL 组的几乎所有分析结果与对照组相似,并且在该组中未观察到明显的病理改变。所得数据表明,SL 可保护肝脏免受 PAC 的有害影响,特别是由于其 TNF-α抑制剂、抗炎、抗凋亡和抗氧化作用。基于这一结果,在使用 PAC 治疗癌症的情况下,可以建议与 SL 一起使用,以防止对健康肝组织的有害影响,并继续不间断和有效地进行治疗。

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