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

被引:15
作者
Hamity, Marta, V [1 ]
White, Stephanie R. [1 ]
Blum, Christopher [1 ,4 ]
Gibson-Corley, Katherine N. [2 ]
Hammond, Donna L. [1 ,3 ]
机构
[1] Univ Iowa, Dept Anesthesia, 25 S Grand Ave,3000 Med Labs, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA
[3] Univ Iowa, Dept Neurosci & Pharmacol, Iowa City, IA 52242 USA
[4] Kansas City Univ, Sch Osteopath Med, Joplin, MO USA
关键词
NIAGEN; Allodynia; Breast cancer; Ki67; Chemotherapy-induced peripheral neuropathy; NAD(+) METABOLISM; BREAST-CANCER; CHEMOTHERAPY; PRECURSOR; SURVIVORS; PAIN;
D O I
10.1097/j.pain.0000000000001924
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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.
引用
收藏
页码:2364 / 2375
页数:12
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