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Zafirlukast in combination with pseudohypericin attenuates spinal cord injury and motor function in experimental mice

Authors Chen XG, Hua F, Wang SG, Xu YY, Yue HT, Sun J

Received 22 October 2017

Accepted for publication 22 March 2018

Published 1 August 2018 Volume 2018:12 Pages 2389—2402

DOI https://doi.org/10.2147/DDDT.S154814

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Qiongyu Guo


Xiao-Gang Chen,1 Fu Hua,2 Shou-Guo Wang,1 Yong-Yi Xu,1 Hai-Tao Yue,1 Jin Sun1

1Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu 223300, People’s Republic of China; 2Department of Gynaecology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu 223300, People’s Republic of China

Background: Biosynthesis of leukotriene (LT) by arachidonic acid involves 5-lipoxygenase (5-LO) as an important precursor. Here, we evaluated the role of pseudohypericin (PHP) for its postulated 5-LO inhibitory activity along with a Cys-LT receptor antagonist zafirlukast (ZFL) against inflammatory response and tissue injury in mice.
Materials and methods: The spinal injury was induced by two-level laminectomy of T6 and T7 vertebrae. The inflammation was assessed by histology, inflammatory mediators by enzyme-linked immunosorbent assay, apoptosis by Annexin-V, FAS staining, terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL) assay and expression of Bax and Bcl-2 by Western blot. Effect on motor recovery of hind limbs was evaluated for 10 days postinjury.
Results: The spinal injury resulted in tissue damage, apoptosis, edema, infiltration of neutrophils with increased expression of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). The spinal tissue showed elevated levels of prostaglandin E2 (PGE2), and LTB4 and increased phosphorylation of injured extracellular signal-regulated kinase-1/2 (ERK1/2). The PHP, ZFL and combination decreased inflammation, tissue injury and infiltration of neutrophils. Treatment also decreased the levels of PGE2, phosphorylation of extracellular signal-regulated kinase-1/2 (pERK 1/2), LT, TNF-α and COX-2 with a marked reduction in apoptosis and improved the motor function.
Conclusion: The present study confirmed 5-LO antagonist activity of PHP and established its neuroprotective role along with ZFL.

Keywords: pseudohypericin, zafirlukast, 5-lipoxygenase, Cys-LT, mice

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