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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Repurposing of Angiotensin-converting-enzyme Inhibitor on Prevention of Post-surgical Tendon Adhesion

Author(s): Hamideh Naimi, Majid Khazaei*, Fariba Sharifnia and Sayyed-Hadi Sayyed-Hosseinian

Volume 30, Issue 11, 2024

Published on: 11 March, 2024

Page: [859 - 867] Pages: 9

DOI: 10.2174/0113816128284671240214080516

Price: $65

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Abstract

Background: Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model.

Methods: Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods.

Results: ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs.

Conclusion: Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.

Keywords: Achilles tendon adhesion, post-surgical tendon adhesion, renin-angiotensin system, angiotensin-converting-enzyme inhibitor, enalapril, extracellular matrix.

[1]
Meier Bürgisser G, Calcagni M, Bachmann E, et al. Rabbit Achilles tendon full transection model – wound healing, adhesion formation and biomechanics at 3, 6 and 12 weeks post-surgery. Biol Open 2016; 5(9): 1324-33.
[http://dx.doi.org/10.1242/bio.020644] [PMID: 27635037]
[2]
Wu YF, Tang JB. Apoptosis in adhesions and the adhesion-tendon gliding interface: Relationship to adhesion-tendon gliding mechanics. J Hand Surg Am 2013; 38(6): 1071-8.
[http://dx.doi.org/10.1016/j.jhsa.2013.03.012] [PMID: 23660197]
[3]
Yan Z, Meng X, Su Y, Chen Y, Zhang L, Xiao J. Double layer composite membrane for preventing tendon adhesion and promoting tendon healing. Mater Sci Eng C 2021; 123: 111941.
[http://dx.doi.org/10.1016/j.msec.2021.111941] [PMID: 33812576]
[4]
Hsu S, Dai LG, Hung YM, Dai NT. Evaluation and characterization of waterborne biodegradable polyurethane films for the prevention of tendon postoperative adhesion. Int J Nanomed 2018; 13: 5485-97.
[http://dx.doi.org/10.2147/IJN.S169825] [PMID: 30271142]
[5]
Fatehi Hassanabad A, Zarzycki AN, Jeon K, et al. Prevention of post-operative adhesions: A comprehensive review of present and emerging strategies. Biomolecules 2021; 11(7): 1027.
[http://dx.doi.org/10.3390/biom11071027] [PMID: 34356652]
[6]
Capella-Monsonís H, Kearns S, Kelly J, Zeugolis DI. Battling adhesions: From understanding to prevention. BMC Biomed Eng 2019; 1(1): 5.
[http://dx.doi.org/10.1186/s42490-019-0005-0] [PMID: 32903353]
[7]
Levi M, van der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109(22): 2698-704.
[http://dx.doi.org/10.1161/01.CIR.0000131660.51520.9A] [PMID: 15184294]
[8]
Chegini N. Peritoneal molecular environment, adhesion formation and clinical implication. Front Biosci 2002; 7: e91-e115.
[PMID: 11897550]
[9]
Asgharzadeh F, Nazari SE, Naeimi H, et al. Phytosomal curcumin and shilajit decrease adhesion bands post-Achilles tendon surgery in animal model. Lett Drug Des Discov 2023; 20
[http://dx.doi.org/10.2174/1570180820666230823091640]
[10]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[11]
Faruqi A, Jain A. Enalapril. St. Petersburg, Florida: StatPearls 2021.
[12]
Herman LL, Padala SA, Annamaraju P, Bashir K. Angiotensin converting enzyme inhibitors (ACEI). St. Petersburg, Florida: StatPearls 2021.
[13]
Brilla, C.G. Renin-angiotensin-aldosterone system and myocardial fibrosis. Cardiovasc Res 2000; 47: 1-3.
[http://dx.doi.org/10.1016/S0008-6363(00)00092-4]
[14]
Dandona P, Dhindsa S, Ghanim H, Chaudhuri A. Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens 2007; 21(1): 20-7.
[http://dx.doi.org/10.1038/sj.jhh.1002101] [PMID: 17096009]
[15]
Ishidoya S, Morrissey J, McCracken R, Reyes A, Klahr S. Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. Kidney Int 1995; 47(5): 1285-94.
[http://dx.doi.org/10.1038/ki.1995.183] [PMID: 7637258]
[16]
Kim S, Ohta K, Hamaguchi A, et al. Angiotensin II type I receptor antagonist inhibits the gene expression of transforming growth factor-beta 1 and extracellular matrix in cardiac and vascular tissues of hypertensive rats. J Pharmacol Exp Ther 1995; 273(1): 509-15.
[PMID: 7714806]
[17]
Arjmand MH, Zahedi-Avval F, Barneh F, et al. Intraperitoneal administration of telmisartan prevents postsurgical adhesion band formation. J Surg Res 2020; 248: 171-81.
[http://dx.doi.org/10.1016/j.jss.2019.10.029] [PMID: 31923833]
[18]
Nazari SE, Naimi H, Sayyed-Hosseinian SH, et al. Effect of angiotensin II pathway inhibitors on post-surgical adhesion band formation: A potential repurposing of old drugs. Injury 2022; 53(11): 3642-9.
[http://dx.doi.org/10.1016/j.injury.2022.08.046] [PMID: 36045032]
[19]
Tang JB, Shi D, Zhang QG. Biomechanical and histologic evaluation of tendon sheath management. J Hand Surg Am 1996; 21(5): 900-8.
[http://dx.doi.org/10.1016/S0363-5023(96)80212-7] [PMID: 8891993]
[20]
De Cavanagh EMV, Piotrkowski B, Basso N, et al. Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J 2003; 17(9): 1096-8.
[http://dx.doi.org/10.1096/fj.02-0063fje] [PMID: 12709417]
[21]
Andrzejczak D, Górska D, Czarnecka E. Influence of enalapril, quinapril and losartan on lipopolysaccharide (LPS)-induced serum concentrations of TNF-alpha, IL-1 beta, IL-6 in spontaneously hypertensive rats (SHR). Pharmacol Rep 2007; 59(9): 437-46.
[22]
Ishiyama N, Moro T, Ishihara K, et al. The prevention of peritendinous adhesions by a phospholipid polymer hydrogel formed in situ by spontaneous intermolecular interactions. Biomaterials 2010; 31(14): 4009-16.
[http://dx.doi.org/10.1016/j.biomaterials.2010.01.100] [PMID: 20149434]
[23]
Moran SL, Ryan CK, Orlando GS, Pratt CE, Michalko KB. Effects of 5-fluorouracil on flexor tendon repair. J Hand Surg Am 2000; 25(2): 242-51.
[http://dx.doi.org/10.1053/jhsu.2000.jhsu25a0242] [PMID: 10722815]
[24]
Lee SY, Chieh HF, Lin CJ, et al. Characteristics of sonography in a rat achilles tendinopathy model: Possible non-invasive predictors of biomechanics. Sci Rep 2017; 7(1): 5100.
[http://dx.doi.org/10.1038/s41598-017-05466-y] [PMID: 28698601]
[25]
Jung H-J, Fisher MB, Woo SL. Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons. Sports Med Arthrosc Rehabil Ther Technol 2009; 1(1): 9.
[PMID: 19457264]
[26]
Nakamura T, Takahashi T, Fukui M, et al. Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats. J Am Soc Nephrol 1995; 5(7): 1492-7.
[http://dx.doi.org/10.1681/ASN.V571492] [PMID: 7703388]
[27]
El Chaar M, Chen J, Seshan SV, et al. Effect of combination therapy with enalapril and the TGF-β antagonist 1D11 in unilateral ureteral obstruction. Am J Physiol Renal Physiol 2007; 292(4): F1291-301.
[http://dx.doi.org/10.1152/ajprenal.00327.2005] [PMID: 17164399]
[28]
Ding L, Liu D, Xu M, et al. Enalapril inhibits tubulointerstitial inflammation and NLRP3 inflammasome expression in BSA-overload nephropathy of rats. Acta Pharmacol Sin 2014; 35(10): 1293-301.
[http://dx.doi.org/10.1038/aps.2014.66] [PMID: 25152022]
[29]
Ghosh SS, Krieg R, Massey HD, et al. Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in % nephrectomized rats: Role of phospholipase and cyclooxygenase. Am J Physiol Renal Physiol 2012; 302(4): F439-54.
[http://dx.doi.org/10.1152/ajprenal.00356.2010] [PMID: 22031851]
[30]
Nikbakht F, Najafipour H, Dabiri SH. The effect of enalapril on inflammation and IL-1β and IL-8 production in chronic arthritis. Daru 2007; 2007: 6.
[31]
Karimian G, Mohammadi-Karakani A, Sotoudeh M, Ghazi-Khansari M, Ghobadi G, Shakiba B. Attenuation of hepatic fibrosis through captopril and enalapril in the livers of bile duct ligated rats. Biomed Pharmacother 2008; 62(5): 312-6.
[http://dx.doi.org/10.1016/j.biopha.2007.10.020] [PMID: 18191530]
[32]
Pahor M. Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats. Hypertension 1991; 18(2): 148-57.
[http://dx.doi.org/10.1161/01.HYP.18.2.148]
[33]
Ghazi-Khansari M, Mohammadi-Karakani A, Sotoudeh M, Mokhtary P, Pour-Esmaeil E, Maghsoud S. Antifibrotic effect of captopril and enalapril on paraquat-induced lung fibrosis in rats. J Appl Toxicol 2007; 27(4): 342-9.
[http://dx.doi.org/10.1002/jat.1212] [PMID: 17265423]

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