Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats

Marta V Hamity; Stephanie R White; Christopher Blum; Katherine N Gibson-Corley; Donna L Hammond

doi:10.1097/j.pain.0000000000001924

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Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats

Journal article

Peer reviewed

Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats

Marta V Hamity, Stephanie R White, Christopher Blum, Katherine N Gibson-Corley and Donna L Hammond

Pain (Amsterdam), Vol.161(10), pp.2364-2375

10/2020

DOI: 10.1097/j.pain.0000000000001924

PMCID: PMC7508763

PMID: 32433266

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Abstract

Nicotinamide riboside (NR) is a vitamin B3 precursor of NAD that blunts diabetic and chemotherapy-induced peripheral neuropathy in preclinical models. This study examined whether NR also blunts the loss of intraepidermal nerve fibers induced by paclitaxel, which is associated with peripheral neuropathy. The work was conducted in female rats with N-methyl-nitrosourea (MNU)-induced tumors of the mammary gland to increase its translational relevance, and to assess the interaction of NR with paclitaxel and NR's effect on tumor growth. Once daily oral administration of 200 mg/kg NR p.o. beginning with the first of 3 i.v. injections of 6.6 mg/kg paclitaxel to tumor-bearing rats significantly decreased paclitaxel-induced hypersensitivity to tactile and cool stimuli, as well as place-escape avoidance behaviors. It also blunted the loss of intraepidermal nerve fibers in tumor-bearing rats, as well as a separate cohort of tumor-naive rats. Unexpectedly, concomitant administration of NR during paclitaxel treatment further decreased tumor growth; thereafter, tumor growth resumed at the same rate as vehicle-treated controls. Administration of NR also decreased the percentage of Ki67-positive tumor cells in these rats. Once daily administration of NR did not seem to alter tumor growth or the percentage of Ki67-positive tumor cells in rats that were not treated with paclitaxel and followed for 3 months. These results further support the ability of NR to play a protective role after nerve injury. They also suggest that NR may not only alleviate peripheral neuropathy in patients receiving taxane chemotherapy, but also offer an added benefit by possibly enhancing its tumor-suppressing effects.

Niacinamide - analogs & derivatives

Peripheral Nervous System Diseases - chemically induced

Animals

Paclitaxel - adverse effects

Rats

Female

Paclitaxel - therapeutic use

Peripheral Nervous System Diseases - drug therapy

Neoplasms - drug therapy

Details

Title: Subtitle: Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats
Creators: Marta V Hamity - Departments of Anesthesia
Stephanie R White - University of Iowa
Christopher Blum - Departments of Anesthesia
Katherine N Gibson-Corley - Pathology and
Donna L Hammond - Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA, United States. C. Blum is now with the Kansas City University School of Osteopathic Medicine, Joplin, MO, United States
Resource Type: Journal article
Publication Details: Pain (Amsterdam), Vol.161(10), pp.2364-2375
DOI: 10.1097/j.pain.0000000000001924
PMID: 32433266
PMCID: PMC7508763
NLM abbreviation: Pain
ISSN: 0304-3959
eISSN: 1872-6623
Publisher: United States
Grant note: S10 OD014165 / NIH HHS P30 CA086862 / NCI NIH HHS R01 AT009705 / NCCIH NIH HHS
Language: English
Date published: 10/2020
Academic Unit: The University of Iowa Institute for Vision Research; Pathology; Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984070587202771

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