Quantitative detection of targeted neurotransmitters in dorsal root ganglia in rats with chronic peripheral neurotoxicity caused by oxaliplatin

Wenling ZHENG; Yanrong CHEN; Juanjuan OU; Houjie LIANG

doi:10.16016/j.1000-5404.201911199

您当前的位置：

首页 >

文章列表页 >

Quantitative detection of targeted neurotransmitters in dorsal root ganglia in rats with chronic peripheral neurotoxicity caused by oxaliplatin

Basic Medicine | 更新时间：2026-01-09

- Quantitative detection of targeted neurotransmitters in dorsal root ganglia in rats with chronic peripheral neurotoxicity caused by oxaliplatin
- Journal of Third Military Medical University Vol. 42, Issue 7, Pages: 684-691(2020)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院肿瘤科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201911199
  CLC： R322.85;R979.1;R996
- Received：25 November 2019，
  
  Revised：2020-02-02，
  
  Published：15 April 2020
- 稿件说明：
移动端阅览
Wenling ZHENG, Yanrong CHEN, Juanjuan OU, et al. Quantitative detection of targeted neurotransmitters in dorsal root ganglia in rats with chronic peripheral neurotoxicity caused by oxaliplatin[J]. Journal of Third Military Medical University, 2020, 42(7): 684-691.
DOI：

Wenling ZHENG, Yanrong CHEN, Juanjuan OU, et al. Quantitative detection of targeted neurotransmitters in dorsal root ganglia in rats with chronic peripheral neurotoxicity caused by oxaliplatin[J]. Journal of Third Military Medical University, 2020, 42(7): 684-691. DOI： 10.16016/j.1000-5404.201911199.

摘要

目的

观察大鼠慢性外周神经毒性模型中奥沙利铂对背根神经节中神经递质类物质浓度的影响。

方法

24只雄性SD大鼠(SPF级)按抽签法完全随机分为2组，每组12只，分别为模型组和对照组。采用多累积剂量、多频次腹腔注射(累积剂量48 mg/m

模拟人体剂量＞1 200 mg/m

)的方法建立慢性外周神经毒性模型，利用神经递质类物质靶标定量检测筛选出背根神经内浓度显著改变的神经递质类物质。

结果

在奥沙利铂累积剂量为48 mg/m

时，可成功构建大鼠慢性外周神经毒性模型；其背根神经节内谷氨酰胺、L-谷氨酸、多巴胺、去甲肾上腺素、3、4-二羟基苯乙酸、香草扁桃酸的浓度较对照组明显增加，尤其以多巴胺及其代谢产物3、4-二羟基苯乙酸的增加最为显著。

结论

奥沙利铂慢性蓄积可导致背根神经节内部分神经递质类物质的浓度发生改变，可能与神经元损伤及慢性外周神经毒性发生有关。

Abstract

Objective

To observe the effects of oxaliplatin on the concentration of neurotransmitters in dorsal root ganglia in a rat model of chronic peripheral neurotoxicity.

Methods

A total of 24 male SD rats (SPF grade) were randomly divided into model group and normal control group (

=12 in each group). The model of chronic peripheral neurotoxicity was established by multiple cumulative doses and multiple intraperitoneal injections (cumulative dose of 48 mg/m

simulated human dose

1 200 mg/m

). The neurotransmitters with significant concentration changes in the dorsal root were screened out by a quantitative detection.

Results

At a cumulative dose

of 48 mg/m

oxaliplatin

a rat model of chronic peripheral neurotoxicity was established successfully. In the dorsal root

the neurotransmitters with obviously increase in concentration were L-glutamine (58.54±10.46 nmol/L

0.05)

L-glutamic acid (43.12±7.76 nmol/L

0.05)

dopamine (0.03±0.02 nmol/L

0.01)

norepinephrine (0.25±0.04 nmol/L

0.05)

3、4-dihydroxyphenylacetic acid (0.41±0.01 nmol/L

0.01)

and vanillylmandelic acid (3.30±0.63 nmol/L

0.05) when compared with the normal control group. Among them

dopamine and its metabolite 3、4-dihydroxyphenylacetic acid were the most significant.

Conclusion

Chronic accumulation of oxaliplatin can cause changes in the concentration of neurotransmitters in the dorsal root ganglia

which may be related to neuronal damage and chronic peripheral neurotoxicity.

关键词

Keywords

references

BEIJERS A J, MOLS F, VREUGDENHIL G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration[J]. Support Care Cancer, 2014, 22(7): 1999-2007. DOI: 10.1007/s00520-014-2242-z.

WOLF S, BARTON D, KOTTSCHADE L, et al . Chemotherapy-induced peripheral neuropathy: prevention and treatmentstrategies[J ] . Eur J Cancer, 2008, 44(11): 1507-1515. DOI: 10.1016/j.ejca.2008.04.018.

GENT P, MASSEY K. An overview of chemotherapy-induced peripheral sensory neuropathy, focusing on oxaliplatin[J]. Int J Palliat Nurs, 2001, 7(7): 354-359. DOI: 10.12968/ijpn.2001.7.7.9020.

ARGYRIOU A A. Updates on oxaliplatin-induced peripheral neurotoxicity (OXAIPN)[J]. Toxics, 2015, 3(2): 187-197. DOI: 10.3390/toxics3020187.

ARGYRIOU A A, POLYCHRONOPOULOS P, ICONOMOU G, et al . A review on oxaliplatin-induced peripheral nerve damage[J ] . Cancer Treat Rev, 2008, 34(4): 368-377. DOI: 10.1016/j.ctrv.2008.01.003.

AHMED K E M, FRØYSA H G, KARLSEN O A, et al . LC-MS/MS based profiling and dynamic modelling of the steroidogenesis pathway in adrenocarcinoma H295R cells[J ] . Toxicol In Vitro, 2018, 52: 332-341. DOI: 10.1016/j.tiv.2018.07.002.

OBWALD A, WANG R, BEUSCHLEIN F, et al . Performance of LC-MS/MS and immunoassay based 24-h urine free cortisol in the diagnosis of Cushing's syndrome[J ] . J Steroid Biochem Mol Biol, 2019, 190: 193-197. DOI: 10.1016/j.jsbmb.2019.04.004.

JAMIESON S M, LIU J, CONNOR B, et al . Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss[J ] . Cancer Chemother Pharmacol, 2005, 56(4): 391-399. DOI: 10.1007/s00280-004-0953-4.

STOJANOVSKA V, MCQUADE R M, FRASER S, et al . Oxaliplatin-induced changes in microbiota, TLR4 + cells and enhanced HMGB1 expression in the murine colon[J ] . PLoS ONE, 2018, 13(6): e0198359. DOI: 10.1371/journal.pone.0198359..

CAVALETTI G, TREDICI G, PETRUCCIOLI M G, et al . Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat[J ] . Eur J Cancer, 2001, 37(18): 2457-2463. DOI: 10.1016/s0959-8049(01)00300-8.

KIM S T, CHUNG Y H, LEE H S, et al . Protective effects of phosphatidylcholine on oxaliplatin-induced neuropathy in rats[J ] . Life Sci, 2015, 130: 81-87. DOI: 10.1016/j.lfs.2015.03.013.

WOLF S, BARTON D, KOTTSCHADE L, et al . Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies[J ] . Eur J Cancer, 2008, 44(11): 1507-1515. DOI: 10.1016/j.ejca.2008.04.018.

CHAPLAN S R, BACH F W, POGREL J W, et al . Quantitative assessment of tactile allodynia in the rat paw[J ] . J Neurosci Methods, 1994, 53(1): 55-63. DOI: 10.1016/0165-0270(94)90144-9.

RENN C L, CAROZZI V A, RHEE P, et al . Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice[J ] . Mol Pain, 2011, 7: 29. DOI: 10.1186/1744-8069-7-29.

SCRENCI D, MCKEAGE M J, GALETTIS P, et al . Relationships between hydrophobicity, reactivity, accumulation and peripheral nerve toxicity of a series of platinum drugs[J ] . Br J Cancer, 2000, 82(4): 966-972. DOI: 10.1054/bjoc.1999.1026.

ARETI A, KOMIRISHETTY P, AKUTHOTA M, et al . Melatonin prevents mitochondrial dysfunction and promotes neuroprotection by inducing autophagy during oxaliplatin-evoked peripheral neuropathy[J ] . J Pineal Res, 2017, 62(3): e12393. DOI: 10.1111/jpi.12393.

SLEIGH J N, WEIR G A, SCHIAVO G. A simple, step-by-step dissection protocol for the rapid isolation of mouse dorsal root Ganglia[J]. BMC Res Notes, 2016, 9: 82. DOI: 10.1186/s13104-016-1915-8.

CARRIEL V, CAMPOS A, ALAMINOS M, et al . Staining methods for normal and regenerative myelin in the nervous system[J ] . Methods Mol Biol, 2017, 1560: 207-218. DOI: 10.1007/978-1-4939-6788-9_15.

LUO F R, WYRICK S D, CHANEY S G. Comparative neurotoxicity of oxaliplatin, ormaplatin, and their biotransformation products utilizing a rat dorsal root Ganglia in vitro explant culture model[J ] . Cancer Chemother Pharmacol, 1999, 44(1): 29-38. DOI: 10.1007/s002800050941.

PULVERS J N, MARX G. Factors associated with the development and severity of oxaliplatin-induced peripheral neuropathy: a systematic review[J]. Asia Pac J Clin Oncol, 2017, 13(6): 345-355. DOI: 10.1111/ajco.12694.

JAYAKUMAR A R, NORENBERG M D. Glutamine synthetase: role in neurological disorders[J]. Adv Neurobiol, 2016, 13: 327-350. DOI: 10.1007/978-3-319-45096-4_13.

DABROWSKA K, SKOWRONSKA K, POPEK M, et al . Roles of glutamate and glutamine transport in Ammonia neurotoxicity: state of the art and question marks[J ] . Endocr Metab Immune Disord Drug Targets, 2018, 18(4): 306-315. DOI: 10.2174/1871520618666171219124427.

NEU J, LI N. Pathophysiology of glutamine and glutamate metabolism in premature infants[J]. Curr Opin Clin Nutr Metab Care, 2007, 10(1): 75-79. DOI: 10.1097/MCO.0b013e328011923c.

NEWSHOLME P, PROCOPIO J, LIMA M M, et al . Glutamine and glutamate: their central role in cell metabolism and function[J ] . Cell Biochem Funct, 2003, 21(1): 1-9. DOI: 10.1002/cbf.1003.

TIAN Y, DU W, CAO S, et al . Systematic analyses of glutamine and glutamate metabolisms across different cancer types[J ] . Chin J Cancer, 2017, 36(1): 88. DOI: 10.1186/s40880-017-0255-y.

SAGHEDDU C, ARONI S, DE FELICE M, et al . Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain[J ] . Neuropharmacology, 2015, 97: 383-393. DOI: 10.1016/j.neuropharm.2015.06.003.

WOOD P B. Role of central dopamine in pain andanalgesia[J]. Expert Rev Neurother, 2008, 8(5): 781-797. DOI: 10.1586/14737175.8.5.781.

YOSHIKAWA M, NISHIYAMA S, TAKAITI O. Metabolism of dopamine prodrug, docarpamine[J]. Hypertens Res, 1995, 18(Suppl 1): S211-S213. DOI: 10.1291/hypres.18.supplementi_s211.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Oxaliplatin suppresses gastric cancer by inducing cuproptosis

Herniation of nucleus pulposus causes pain and dorsal root ganglion sympathetic sprouting in rats

Silencing pregnane X receptor improves chemosensitivity of colon cancer LS174T cells to oxaliplatin

Oxaliplatin long-circulating liposomes improves apoptosis of human colorectal cancer SW480 cells

Expression change of P2X₃ receptor in spinal dorsal horn and dorsal root ganglion in inflammatory pain rats

Related Author

YANG Hong

XIONG Mengyuan

ZHANG Liyong

HAN Xiao

DENG Boshao

WANG Lulu

CHEN Jian

SHI Yan

Related Institution

Department of General Surgery， First Affiliated Hospital（Southwest Hospital）, College of Basic Medical Sciences， Army Medical University （Third Military Medical University）

Department of Immunology, College of Basic Medical Sciences， Army Medical University （Third Military Medical University）

⁰