Department of Neurosurgery, Private Buhara Hospital, Erzurum, Turkey.
Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240, Erzurum, Turkey.
Neurochem Res. 2021 Feb;46(2):379-395. doi: 10.1007/s11064-020-03174-0. Epub 2020 Nov 17.
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.
紫杉醇（PTX）是一种常用于治疗实体瘤的抗肿瘤药物，已知其会引起剂量限制的周围神经毒性。本研究旨在评估姜黄素（CUR）对大鼠紫杉醇诱导的脊髓和坐骨神经损伤的保护作用。大鼠腹腔内给予紫杉醇（2mg/kg，BW）连续 5 天，随后给予 CUR（100 和 200mg/kg，BW 每日在玉米油中）口服 10 天。我们的结果表明，CUR 显著降低了脊髓和坐骨神经中 NF-κB、TNF-α、IL-6、iNOS 和 GFAP 的 mRNA 表达水平，而增加了 Nrf2、HO-1 和 NQO1 的水平。此外，CUR 通过增加 Bcl-2 和 Bcl-xL，减少 p53、caspase-3、Apaf-1、LC3A、LC3B 和 beclin-1 的 mRNA 表达水平，抑制了凋亡和自噬途径的激活。结果表明，CUR 通过 LFB 染色和 H&E 染色也维持了脊髓和坐骨神经的组织学结构和完整性。CUR 给药后，紫杉醇诱导的脊髓组织中 8-OHdG、caspase-3 和 LC3B 的免疫组化表达降低。总之，我们的研究结果表明，CUR 对大鼠紫杉醇诱导的脊髓和坐骨神经损伤具有保护作用。
