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Cancer Chemotherapy and Pharmacology

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14.08.2020 | Original Article

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

verfasst von: Mina Khalilzadeh, Fereshteh Hassanzadeh, Helia Aghamiri, Ahmad Reza Dehpour, Hamed Shafaroodi

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2020

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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.

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Titel: Aripiprazole prevents from development of vincristine-induced neuropathic nociception by limiting neural NOS overexpression and NF-kB hyperactivation
verfasst von: Mina Khalilzadeh
Fereshteh Hassanzadeh
Helia Aghamiri
Ahmad Reza Dehpour
Hamed Shafaroodi
Publikationsdatum: 14.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2020
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04127-8

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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

Abstract

Purpose

Methods

Results

Conclusion

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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