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Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats
Gene ( IF 2.6 ) Pub Date : 2020-10-15 , DOI: 10.1016/j.gene.2020.145239
Ahmet Yardım , Sefa Kucukler , Selçuk Özdemir , Selim Çomaklı , Cuneyt Caglayan , Fatih Mehmet Kandemir , Hamit Çelik

Docetaxel (DTX) is a chemotherapeutic agent used in the treatment of various malignancies but is often associated with central and peripheral neurotoxicity. The aim of this study was to investigate the neuroprotective effect of silymarin (SLM) against DTX-induced central and peripheral neurotoxicities in rats. Rats received 25 and 50 mg/kg body weight SLM orally for seven consecutive days after receiving a single injection of 30 mg/kg body weight DTX on the first day. SLM significantly decreased brain lipid peroxidation level and ameliorated brain glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in DTX-administered rats. SLM attenuated levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activity of p38α mitogen-activated protein kinase (p38α MAPK) whereas caused an increase in levels of neural cell adhesion molecule (NCAM) in the brain and sciatic nerve of DTX-induced rats. In addition, SLM improved the histological structure of the brain and sciatic nerve tissues and decreased the expression of c-Jun N-terminal kinase (JNK) in the sciatic nerve whereas increased cyclic AMP response element binding protein (CREB) expression in the brain induced by DTX. Additionally, SLM markedly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and B-cell lymphoma-2 (Bcl-2) and downregulated the expression of Bcl-2 associated X protein (Bax) in the brain and sciatic nerve tissues of DTX-induced rats. Our results show that SLM can protect DTX-induced brain and sciatic nerve injuries by enhancing the antioxidant defense system and suppressing apoptosis and inflammation.



中文翻译:

水飞蓟素通过减少大鼠的氧化应激,炎症和细胞凋亡减轻多西他赛诱导的中枢和周围神经毒性

多西他赛(DTX)是用于治疗各种恶性肿瘤的化学治疗剂,但通常与中枢和周围神经毒性有关。这项研究的目的是调查水飞蓟素(SLM)对DTX诱导的大鼠中枢和周围神经毒性的神经保护作用。在第一天单次注射30 mg / kg体重的DTX后,大鼠连续7天口服25和50 mg / kg体重的SLM。SLM可以显着降低DTX给药大鼠的脑脂质过氧化水平并改善脑谷胱甘肽(GSH),超氧化物歧化酶(SOD),过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)活性。SLM减弱了核因子κB(NF-κB),肿瘤坏死因子-α(TNF-α)的水平,胶质纤维酸性蛋白(GFAP)和p38α丝裂原活化蛋白激酶(p38αMAPK)的活性,却导致DTX诱导的大鼠的大脑和坐骨神经中神经细胞粘附分子(NCAM)的水平增加。此外,SLM改善了大脑和坐骨神经组织的组织学结构,并降低了坐骨神经中c-Jun N末端激酶(JNK)的表达,而诱导的脑中环AMP反应元件结合蛋白(CREB)的表达增加由DTX。此外,SLM显着上调了核因子红系2相关因子2(Nrf2),血红素加氧酶1(HO-1)和B细胞淋巴瘤2(Bcl-2)的表达,并下调了Bcl-2的表达。 DTX诱导的大鼠的大脑和坐骨神经组织中有2种相关的X蛋白(Bax)。

更新日期:2020-10-16
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