Aripiprazole prevents from development of vincristine-induced neuropathic nociception by limiting neural NOS overexpression and NF-kB hyperactivation

Khalilzadeh, M. and Hassanzadeh, F. and Aghamiri, H. and Dehpour, A.R. and Shafaroodi, H. (2020) Aripiprazole prevents from development of vincristine-induced neuropathic nociception by limiting neural NOS overexpression and NF-kB hyperactivation. Cancer Chemotherapy and Pharmacology, 86 (3). pp. 393-404.

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Abstract

Purpose: Increased nitric oxide (NO) synthesis and NF-kB activation have been shown as critical players in the pathophysiology of vincristine-induced peripheral neuropathy. Consistently, neural nitric oxide synthase (nNOS) inhibitors alleviated the neuropathic pain. Previous studies demonstrated that aripiprazole is capable of modulating NO synthesis and also has been reported its modulatory effect on NF-kB activity. Methods: Aripiprazole was administered daily to the male Wistar rats at the same time with establishing neuropathic model by I.P. injection of vincristine every 2 days, over 2 weeks. Efficacy of aripiprazole in suppressing the development of neuropathy was evaluated by assessing changes in body weight, mechanical threshold, withdrawal latency, sciatic nerve conduction velocity (SNCV), and compound motor action potential (CMAP) characteristics. Expression of nNOS and NF-kB activation were evaluated by western blotting Results: Rats receiving aripiprazole during neuropathy establishment period demonstrated a normal weight gain pattern, a significantly higher mechanical withdrawal threshold, and SNCV compared to vincristine-treated group. Furthermore, the amplitude and area of CMAP were significantly higher in aripiprazole group. Western blotting demonstrated a significantly reduced expression of nNOS and NF-kB activation in dorsal root ganglia of aripiprazole co-treated rats. Conclusion: In conclusion, aripiprazole effectively prevents from vincristine-induced neuropathy by limiting nNOS overexpression and NF-kB hyperactivation. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: aripiprazole; immunoglobulin enhancer binding protein; nitric oxide synthase; vincristine, animal experiment; animal model; Article; body weight; body weight gain; body weight loss; controlled study; drug efficacy; gene overexpression; in vivo study; male; mechanical allodynia; muscle action potential; nerve conduction velocity; neuromodulation; neuroprotection; nociception; nonhuman; peripheral neuropathy; priority journal; protein expression; rat; sciatic nerve; spinal ganglion; Western blotting; Wistar rat
Subjects: QV Pharmacology
Depositing User: eprints admin
Date Deposited: 08 Jun 2021 07:20
Last Modified: 08 Jun 2021 07:20
URI: http://eprints.iums.ac.ir/id/eprint/34140

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