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Protective Effects of Curcumin Against Paclitaxel-Induced Spinal Cord and Sciatic Nerve Injuries in Rats
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-11-17 , DOI: 10.1007/s11064-020-03174-0
Ahmet Yardım 1 , Fatih Mehmet Kandemir 2 , Selim Çomaklı 3 , Selçuk Özdemir 4 , Cuneyt Caglayan 5 , Sefa Kucukler 2 , Hamit Çelik 6
Affiliation  

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.



中文翻译:


姜黄素对紫杉醇引起的大鼠脊髓和坐骨神经损伤的保护作用



紫杉醇 (PTX) 是一种常用于治疗实体瘤的抗肿瘤药物,已知会引起剂量限制性周围神经毒性。本研究旨在评估姜黄素 (CUR) 对 PTX 诱导的大鼠脊髓和坐骨神经损伤的保护作用。前连续 5 天对大鼠腹腔注射 PTX(2 mg/kg,BW),随后口服 CUR(100 和 200 mg/kg,每天 BW,溶于玉米油),持续 10 天。我们的结果表明,CUR 显着降低 PTX 脊髓和坐骨神经中 NF-κB、TNF-α、IL-6、iNOS 和 GFAP mRNA 表达水平,同时导致 Nrf2、HO-1 和 NQO1 水平增加诱导大鼠。此外,CUR 通过增加 Bcl-2 和 Bcl-xL,降低 p53、caspase-3、Apaf-1、LC3A、LC3B 和 beclin-1 mRNA 表达水平来抑制细胞凋亡和自噬途径的激活。结果表明,通过 LFB 染色和 H&E 染色,CUR 还保持了脊髓和坐骨神经的组织学结构和完整性。 CUR给药后,PTX诱导的脊髓组织中8-OHdG、caspase-3和LC3B的免疫组织化学表达降低。综上所述,我们的研究结果表明,CUR 对 PTX 诱导的大鼠脊髓和坐骨神经损伤具有保护作用。

更新日期:2020-11-17
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