The neuroprotective effect of pterostilbene on oxaliplatin-induced peripheral neuropathy via its anti-inflammatory, anti-oxidative and anti-apoptotic effects: Comparative study with celecoxib.

Autor: Abd-Elmawla MA; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Abdelalim E; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: eman.mahdy@pharma.cu.edu.eg., Ahmed KA; Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt., Rizk SM; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Feb 15; Vol. 315, pp. 121364. Date of Electronic Publication: 2023 Jan 05.
DOI: 10.1016/j.lfs.2022.121364
Abstrakt: Background: Oxaliplatin is one of the first-line drugs in solid tumors treatment. However, neuropathy is a devastating side effect leading to poor compliance and treatment cessation.
Aim: The current study explored pterostilbene plausible neuroprotective effects aiming to ascertain the potential mechanisms involved in relieving oxaliplatin-induced peripheral neuropathy (OIPN) and investigating whether pterostilbene and celecoxib combination could show better relief.
Main Methods: Rats were divided into six groups; control, pterostilbene (40 mg/kg/day, p.o. for 5 weeks), oxaliplatin (4 mg/kg, i.p. twice per week for 4.5 weeks), celecoxib (30 mg/kg/day, p.o. for 5 weeks) and combination of pterostilbene and celecoxib. Behavioral tests and histopathological analysis of sciatic nerves were done. MAPKs, cytokines, COX-2, and PGE 2 gene and protein expressions were estimated using qRT-PCR, western, and ELISA techniques. Malondialdehyde (MDA) and total antioxidant capacity (TAC) were assessed by colorimetric assay while apoptotic markers by immunohistochemical analysis and qRT-PCR.
Key Findings: The study revealed that pterostilbene and celecoxib averted oxaliplatin-induced behavioral and motor impairments along with restoration of histopathological changes. Moreover, pterostilbene and celecoxib have significantly attenuated sciatic nerve: p38 MAPK, JNK, ERK1/2, NF-κB, COX-2, PGE 2 , TNF-α, and interleukins levels. Pterostilbene and celecoxib have reduced caspase-3, Bax, and MDA while increasing Bcl-2 level and TAC.
Significance: Altogether, Pterostilbene mitigates OIPN by interrupting the vicious cycle of inflammation, oxidation, and apoptosis. Furthermore, pterostilbene and celecoxib show comparable attenuation on MAPKs cascades, inflammatory cytokines, oxidative and apoptotic markers. Likewise, co-administration of pterostilbene and celecoxib shows further relief of neuropathic pain.
Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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