Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats.
Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats.
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DOI：
10.1097/j.pain.0000000000001924
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发表时间：
2020-10
期刊：
影响因子：
7.4
通讯作者：
Hammond DL
中科院分区：
文献类型：
--
作者：
Hamity MV;White SR;Blum C;Gibson-Corley KN;Hammond DL
烟酰胺核苷（NR）是NAD+的维生素B3前体，在临床前模型中可以减弱糖尿病和化疗诱导的周围神经病变。本研究考察了NR是否也能减弱紫杉醇引起的表皮内神经纤维（IENF）的损失，这种损失与周围神经病变有关。本研究在n -甲基亚硝基脲（MNU）诱导乳腺肿瘤的雌性大鼠中进行，以增加其翻译相关性，并评估NR与紫杉醇的相互作用以及NR对肿瘤生长的影响。荷瘤大鼠每日口服200 mg/kg NR p.o.，以3次静脉注射6.6 mg/kg紫杉醇的第一次开始，可显著降低紫杉醇诱导的触觉和低温刺激超敏反应，以及场所逃避回避行为。它还能减弱荷瘤大鼠以及tumor-naïve大鼠体内IENF的丧失。出乎意料的是，紫杉醇治疗期间同时给予NR进一步降低了肿瘤生长；此后，肿瘤恢复生长的速度与用载体治疗的对照组相同。NR也降低了这些大鼠中ki67阳性肿瘤细胞的百分比。在未接受紫杉醇治疗并随访三个月的大鼠中，每日给药NR似乎没有改变肿瘤生长或ki67阳性肿瘤细胞的百分比。这些结果进一步支持NR在神经损伤后发挥保护作用的能力。他们还认为NR不仅可以缓解接受紫杉烷化疗的患者的周围神经病变，而且还可能通过增强其肿瘤抑制作用提供额外的益处。在荷瘤大鼠中，烟酰胺核苷可以减弱紫杉醇引起的异位性疼痛和表皮内神经纤维的丢失，并意外增强紫杉醇对肿瘤生长的抑制作用。
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 (IENF) 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 three 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 IENF in tumor-bearing rats, as well as a separate cohort of tumor-naïve 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 appear to alter tumor growth or the percentage of Ki67-positive tumor cells in rats that were not treated with paclitaxel and followed for three months. These results further support the ability of NR to play a protective role following 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. In tumor-bearing rats, nicotinamide riboside blunts the allodynia and loss of intraepidermal nerve fibers induced by paclitaxel, and unexpectedly enhances paclitaxel’s suppression of tumor growth.
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DOI：
10.1126/science.aad5168
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cambronne XA;Stewart ML;Kim D;Jones-Brunette AM;Morgan RK;Farrens DL;Cohen MS;Goodman RH
通讯作者：
Goodman RH
影响因子：
6
作者：
BALFOUR, DJK
通讯作者：
BALFOUR, DJK
影响因子：
64.8
作者：
Chowdhry, Sudhir;Zanca, Ciro;Mischel, Paul S.
通讯作者：
Mischel, Paul S.
影响因子：
11.2
作者：
Allen JK;Armaiz-Pena GN;Nagaraja AS;Sadaoui NC;Ortiz T;Dood R;Ozcan M;Herder DM;Haemmerle M;Gharpure KM;Rupaimoole R;Previs RA;Wu SY;Pradeep S;Xu X;Han HD;Zand B;Dalton HJ;Taylor M;Hu W;Bottsford-Miller J;Moreno-Smith M;Kang Y;Mangala LS;Rodriguez-Aguayo C;Sehgal V;Spaeth EL;Ram PT;Wong STC;Marini FC;Lopez-Berestein G;Cole SW;Lutgendorf SK;De Biasi M;Sood AK
通讯作者：
Sood AK
影响因子：
9.8
作者：
Currie, Gillian L.;Angel-Scott, Helena N.;Sena, Emily S.
通讯作者：
Sena, Emily S.