Experimental study in prevention of epidural fibrosis in rats by local application of hydroxyurea

LOU Linbing; ZHU Sibo; XU Lei; DAI Jihang; WANG Yongxiang

doi:10.7619/jcmp.20232719

Journal of Clinical Medicine in Practice > 2023 > 27(21): 32-36. > DOI: 10.7619/jcmp.20232719

LOU Linbing, ZHU Sibo, XU Lei, DAI Jihang, WANG Yongxiang. Experimental study in prevention of epidural fibrosis in rats by local application of hydroxyurea[J]. Journal of Clinical Medicine in Practice, 2023, 27(21): 32-36. DOI: 10.7619/jcmp.20232719

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Experimental study in prevention of epidural fibrosis in rats by local application of hydroxyurea

LOU Linbing^{1, 2},
ZHU Sibo^{1, 2},
XU Lei^{2, 3},
DAI Jihang^{2, 3},
WANG Yongxiang^{2, 3, ,}

1.
Graduate School of Dalian Medical University, Dalian, Liaoning, 116000
2.
Department of Orthopedics, Subei People′s Hospital of Dalian Medical University, Yangzhou, Jiangsu, 225001
3.
School of Clinical Medicine of Yangzhou University, Yangzhou, Jiangsu, 225001

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Received Date: August 27, 2023
Revised Date: October 11, 2023
Available Online: November 23, 2023

Graphical Abstract

Abstract

Abstract

Objective
To explore the efficacy of postoperative topical preventive application of hydroxyurea (HU) in the rats with laminectomy.
Methods
A total of 36 8-week SD rats were selected and randomly divided into group A (controls), group B (15 mg/mL HU) and group C (30 mg/mL HU). A laminectomy model was prepared; after exposing the dura mater, the surgical area was closed layer by layer after flushing with physiological saline in the group A, while in the group B and the group C, different concentrations of HU cotton pads were soaked and placed in the surgical area for 5 minutes before removal, and the surgical area was closed layer by layer. Change in spinal cord scores of rats before and after surgery was observed. At 4 weeks after surgery, the postoperative epidural adhesions were evaluated through macroscopic observation, hematoxylin eosin (HE) staining, fibroblast counting, Sirius red staining and immunohistochemical staining.
Results
There was no significant difference in the spinal cord scores of rats before and after surgery among the three groups (P>0.05). Macroscopic observation and HE staining showed that compared with the group A, the degrees of epidural adhesion in the surgical area of rats in the group B and the group C were significantly reduced. Image J was used to count fiber cells in each group, and compared with the group A, the number of fibroblasts in the group B and the group C decreased significantly in a concentration dependent manner (P < 0.001 or P < 0.000 1); compared with the group B, the number of fibroblasts in the group C was significantly lower (P < 0.01). Sirius red staining showed a significant decrease in type Ⅰ collagen fibers expression and a significant increase in type Ⅲ collagen fiber expression in the group B and the group C.
Conclusion
Postoperative topical application of HU in the rats with laminectomy can slow down the occurrence of epidural fibrosis.
- hydroxyurea,
- epidural fibrosis,
- laminectomy,
- prevention,
- topical application,
- rats

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References (33)

References

[1]	SEBAALY A, LAHOUD M J, RIZKALLAH M, et al. Etiology, evaluation, and treatment of failed back surgery syndrome[J]. Asian Spine J, 2018, 12(3): 574-585. doi: 10.4184/asj.2018.12.3.574
[2]	WAGUESPACK A, SCHOFFERMAN J, SLOSAR P, et al. Etiology of long-term failures of lumbar spine surgery[J]. Pain Med, 2002, 3(1): 18-22. doi: 10.1046/j.1526-4637.2002.02007.x
[3]	THOMSON S. Failed back surgery syndrome - definition, epidemiology and demographics[J]. Br J Pain, 2013, 7(1): 56-59. doi: 10.1177/2049463713479096
[4]	BABER Z, ERDEK M A. Failed back surgery syndrome: current perspectives[J]. J Pain Res, 2016, 9: 979-987. doi: 10.2147/JPR.S92776
[5]	BATEMAN D K, MILLHOUSE P W, SHAHI N, et al. Anterior lumbar spine surgery: a systematic review and meta-analysis of associated complications[J]. Spine J, 2015, 15(5): 1118-1132. doi: 10.1016/j.spinee.2015.02.040
[6]	HOPPENSTEIN R. A new approach to the failed, failed back syndrome[J]. Spine, 1980, 5(4): 371-379. doi: 10.1097/00007632-198007000-00011
[7]	张飞飞, 董有海. 椎板切除术术后硬膜外纤维化预防的研究进展[J]. 脊柱外科杂志, 2017, 15(4): 243-248. doi: 10.3969/j.issn.1672-2957.2017.04.010
[8]	冯明宣, 洪盾. 腰椎板切除术后硬膜外粘连预防方法的研究进展[J]. 中国骨伤, 2015, 28(11): 1064-1068. doi: 10.3969/j.issn.1003-0034.2015.11.019
[9]	TIMSON J. Hydroxyurea[J]. Mutat Res, 1975, 32(2): 115-132. doi: 10.1016/0165-1110(75)90002-0
[10]	HAIJER F, KOETS-SHAJARI S, HEEGSMA J, et al. Hydroxyurea attenuates hepatic stellate cell proliferation in vitro and liver fibrogenesis in vivo[J]. FASEB J, 2023, 37(9): e23124. doi: 10.1096/fj.202300920R
[11]	BOYD A S, NELDNER K H. Hydroxyurea therapy[J]. J Am Acad Dermatol, 1991, 25(3): 518-524. doi: 10.1016/0190-9622(91)70233-R
[12]	MORTON D, REED L, HUANG W H, et al. Toxicity of hydroxyurea in rats and dogs[J]. Toxicol Pathol, 2015, 43(4): 498-512. doi: 10.1177/0192623314559103
[13]	BASSO D M, BEATTIE M S, BRESNAHAN J C. A sensitive and reliable locomotor rating scale for open field testing in rats[J]. J Neurotrauma, 1995, 12(1): 1-21. doi: 10.1089/neu.1995.12.1
[14]	RYDELL N. Decreased granulation tissue reaction after installment of hyaluronic acid[J]. Acta Orthop Scand, 1970, 41(3): 307-311. doi: 10.3109/17453677008991516
[15]	LEE J, SHIN J S, LEE Y J, et al. Long-term course of failed back surgery syndrome (FBSS) patients receiving integrative Korean medicine treatment: a 1 year prospective observational multicenter study[J]. PLoS One, 2017, 12(1): e0170972. doi: 10.1371/journal.pone.0170972
[16]	EPTER R S, HELM S 2nd, HAYEK S M, et al. Systematic review of percutaneous adhesiolysis and management of chronic low back pain in post lumbar surgery syndrome[J]. Pain Physician, 2009, 12(2): 361-378.
[17]	BOSSCHER H A, HEAVNER J E. Incidence and severity of epidural fibrosis after back surgery: an endoscopic study[J]. Pain Pract, 2010, 10(1): 18-24. doi: 10.1111/j.1533-2500.2009.00311.x
[18]	TANNOURY T, KEMPEGOWDA H, HADDADI K, et al. Complications associated with minimally invasive anterior to the psoas (ATP) fusion of the lumbosacral spine[J]. Spine, 2019, 44(19): E1122-E1129. doi: 10.1097/BRS.0000000000003071
[19]	LI X L, WANG S G, DAI J H, et al. Homoharringtonine prevents surgery-induced epidural fibrosis through endoplasmic reticulum stress signaling pathway[J]. Eur J Pharmacol, 2017, 815: 437-445. doi: 10.1016/j.ejphar.2017.09.027
[20]	YANG L, ZHENG S N, GE D W, et al. LncRNA-COX2 inhibits fibroblast activation and epidural fibrosis by targeting EGR1[J]. Int J Biol Sci, 2022, 18(4): 1347-1362. doi: 10.7150/ijbs.67974
[21]	JIN Z, SUN J P, SONG Z Y, et al. Neutrophil extracellular traps promote scar formation in post-epidural fibrosis[J]. NPJ Regen Med, 2020, 5(1): 19. doi: 10.1038/s41536-020-00103-1
[22]	DING Q, WEI Q, SHENG G H, et al. The preventive effect of decorin on epidural fibrosis and epidural adhesions after laminectomy[J]. Front Pharmacol, 2021, 12: 774316. doi: 10.3389/fphar.2021.774316
[23]	CAO Y L, CHEN H, SUN Y, et al. Quercetin inhibits fibroblasts proliferation and reduces surgery-induced epidural fibrosis via the autophagy-mediated PI3K/Akt/mTOR pathway[J]. Bioengineered, 2022, 13(4): 9973-9986. doi: 10.1080/21655979.2022.2062530
[24]	BOZKURT I, KAZANCI A, GURCAN O, et al. Spinal epidural fibrosis following hemostatic agent employment[J]. Br J Neurosurg, 2023, 37(2): 137-141. doi: 10.1080/02688697.2021.1950627
[25]	LUCÍA R V, JOAQUÍN M. An animal model for assessing the effects of hydroxyurea exposure suggests that the administration of this agent to pregnant women and young infants may not be as safe as we thought[J]. Int J Mol Sci, 2018, 19(12): 3986. doi: 10.3390/ijms19123986
[26]	WARE R E. Hydroxycarbamide: clinical aspects[J]. C R Biol, 2013, 336(3): 177-182. doi: 10.1016/j.crvi.2012.09.006
[27]	HAIJER F, KOETS-SHAJARI S, HEEGSMA J, et al. Hydroxyurea attenuates hepatic stellate cell proliferation in vitro and liver fibrogenesis in vivo[J]. FASEB J, 2023, 37(9): e23124. doi: 10.1096/fj.202300920R
[28]	WOO G H, BAK E J, NAKAYAMA H, et al. Molecular mechanisms of hydroxyurea(HU)-induced apoptosis in the mouse fetal brain[J]. Neurotoxicol Teratol, 2006, 28(1): 125-134. doi: 10.1016/j.ntt.2005.08.002
[29]	ZHOU Y, LU Q L. Hydroxyurea protects against diabetic cardiomyopathy by inhibiting inflammation and apoptosis[J]. Biomedecine Pharmacother, 2022, 153: 113291. doi: 10.1016/j.biopha.2022.113291
[30]	MUSIAŁEK M W, RYBACZEK D. Hydroxyurea-the good, the bad and the ugly[J]. Genes, 2021, 12(7): 1096. doi: 10.3390/genes12071096
[31]	LEBENSBURGER J D, PESTINA T I, WARE R E, et al. Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model[J]. Haematologica, 2010, 95(9): 1599-1603. doi: 10.3324/haematol.2010.023325
[32]	MCGANN P T, WARE R E. Hydroxyurea therapy for sickle cell anemia[J]. Expert Opin Drug Saf, 2015, 14(11): 1749-1758. doi: 10.1517/14740338.2015.1088827
[33]	REES D C. Hydroxyurea: coming to conclusions on safety[J]. Blood, 2021, 137(6): 728-729. doi: 10.1182/blood.2020008803

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Experimental study in prevention of epidural fibrosis in rats by local application of hydroxyurea

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