Protective Effects of Curcumin Against Paclitaxel-Induced Spinal Cord and Sciatic Nerve Injuries in Rats
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ORIGINAL PAPER
Protective Effects of Curcumin Against Paclitaxel-Induced Spinal Cord and Sciatic Nerve Injuries in Rats Ahmet Yardım1 · Fatih Mehmet Kandemir2 · Selim Çomaklı3 · Selçuk Özdemir4 · Cuneyt Caglayan5 · Sefa Kucukler2 · Hamit Çelik6 Received: 11 July 2020 / Revised: 5 November 2020 / Accepted: 10 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause doselimiting 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. Keywords Apoptosis · Curcumin · Inflammation · Paclitaxel · Peripheral neurotoxicity
Introduction
* Fatih Mehmet Kandemir [email protected] * Cuneyt Caglayan [email protected] 1
Department of Neurosurgery, Private Buhara Hospital, Erzurum, Turkey
2
Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240 Erzurum, Turkey
3
Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, 25240 Erzurum, Turkey
4
Department of Genetics, Faculty of Veterinary Medicine, Atatürk University, 25240 Erzurum, Turkey
5
Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, 12000 Bingöl, Turkey
6
Department of Neurology, Private Buhara Hospital, Erzurum, Turkey
Chemotherapy-induced peripheral neuropathy is a common side effect of several anti-cancer agents, such as taxanes (docetaxel, paclitaxel), platinum compounds (cisplatin, oxaliplatin, and carboplatin), vinca alkaloids (vinblastine, vincristine) and bortezomib [1, 2]. A common non-hematological side effect of these agents is peripheral neuropathy [3]. Paclitaxel (PTX) is a highly effective and widely used chemotherapeutic agent, particularly in the treatment of breast, ovarian, bladder, lung, and other types of solid tumor cancers [4, 5]. PTX vigorou
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