Abstract
The current study examines the effects of linalool in preventing postoperative abdominal adhesions. Twenty male Wistar rats were randomly divided into four groups. (1) Sham: in this group, the abdomen was approached, and without any manipulations, it was sutured. (2) Control: rats in this group underwent a surgical procedure to induce adhesions. This involved making three incisions on the right abdominal side and removing a 1×1-cm piece of the peritoneum on the left abdominal side. (3) Treatment groups: these groups underwent the same surgical procedure as the control group to induce adhesions. Animals in these groups received linalool orally with doses of 50 and 100 mg/kg, respectively, for a period of 14 days. Moreover, rats in the sham and control groups received normal saline via gavage for 14 days. The evaluation of TNF-α, TGF-β, VEGF, and caspase 3 was performed using western blot and IHC methods. Furthermore, oxidative stress biomarkers such as MDA, TAC, GSH, and NO were assessed in the peritoneal adhesion tissue. The findings revealed that linalool significantly reduced peritoneal adhesions by reducing TNF-α, TGF-β, VEGF, and caspase 3 levels. Moreover, MDA concentration was significantly decreased, while NO, TAC, and GSH levels were notably increased. Overall, linalool was effective in preventing adhesion formation and reduced inflammation, angiogenesis, apoptosis, and oxidative stress. Therefore, linalool as a potent antioxidant is suggested for reducing postoperative adhesions in rats.
Graphical Abstract
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References
Altinoz E, Oner Z, Elbe H, Uremis N, Uremis M (2022) Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress. Drug Chem Toxicol 45:2024–2030
An Q, Ren J-N, Li X, Fan G, Qu S-S, Song Y, Li Y, Pan S-Y (2021) Recent updates on bioactive properties of linalool. Food Funct 12:10370–10389
Askari VR, Rahimi VB, Zamani P, Fereydouni N, Rahmanian-Devin P, Sahebkar AH, Rakhshandeh H (2018) Evaluation of the effects of Iranian propolis on the severity of post operational-induced peritoneal adhesion in rats. Biomed Pharmacother 99:346–353
Azadi H, Davoodabadi A, Akbari H, Benafsheh HR, Norroddini M, Hajian A (2020) Effect of pimecrolimus on postoperative peritoneal adhesions in rat: an experimental study. Int J Surg Open 24:156–160
Bayhan Z, Zeren S, Kocak FE, Kocak C, Akcılar R, Kargı E, Tiryaki C, Yaylak F, Akcılar A (2016) Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model. J Surg Res 201:348–355
Bi J, Zhang S, Du Z, Zhang J, Deng Y, Liu C, Zhang J (2017) Peripheral serotonin regulates postoperative intra-abdominal adhesion formation in mice. Sci. Rep 7:10001
Bilgi A, Terek MC, Yigitturk G, Taskıran D, İlgen O, Hortu İ (2021) Is there any effect of lycopene’s preventing peritoneal adhesion formation in rats: an experimental study. Authorea Preprints
Fang C-C, Chou T-H, Huang J-W, Lee C-C, Chen S-C (2018) The small molecule inhibitor QLT-0267 decreases the production of fibrin-induced inflammatory cytokines and prevents post-surgical peritoneal adhesions. Sci. Rep 8:9481
Fatehi Hassanabad A, Zarzycki AN, Jeon K, Dundas JA, Vasanthan V, Deniset JF, Fedak PW (2021) Prevention of post-operative adhesions: a comprehensive review of present and emerging strategies. Biomol 11:1027
Ghadiri M, Baradaran Rahimi V, Moradi E, Hasanpour M, Clark CC, Iranshahi M, Rakhshandeh H, Askari VR (2021) Standardised pomegranate peel extract lavage prevents postoperative peritoneal adhesion by regulating TGF-β and VEGF levels. Inflammopharmacology 29:855–868
Holmdahl L, Al-Jabreen M, Risberg B (1994) Experimental models for quantitative studies on adhesion formation in rats and rabbits. Eur Surg Res 26:248–256
Hosseini M, Boskabady MH, Khazdair MR (2021) Neuroprotective effects of Coriandrum sativum and its constituent, linalool: a review. AJP 11:436
Jamshidi-Adegani F, Vakilian S, Al-Kindi J, Rehman NU, Alkalbani L, Al-Broumi M, Al-Wahaibi N, Shalaby A, Al-Sabahi J, Al-Harrasi A (2022) Prevention of post-surgical adhesion bands by local administration of frankincense n-hexane extract. J Tradit Complement Med 12:367–374
Kakanezhadi A, Rezaei M, Raisi A, Dezfoulian O, Davoodi F, Ahmadvand H (2022) Rosmarinic acid prevents post-operative abdominal adhesions in a rat model. Sci. Rep 12:18593
Kazemi K, Hosseinzadeh A, Shahriarirad R, Nikeghbalian S, Kamran H, Hosseinpour P, Tanideh N, Jamshidi K (2022) Comparison of oral sirolimus, prednisolone, and combination of both in experimentally induced peritoneal adhesion. J Surg Res 276:168–173
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. J Pharmacol Pharmacother 1:94–99
Kraemer B, Wallwiener C, Rajab TK, Brochhausen C, Wallwiener M, Rothmund R (2014) Standardised models for inducing experimental peritoneal adhesions in female rats. Biomed Res Int 435056
Liu W, Wu F, Bi X, Hou L, Wang C, Li Y, Zeng Z, Xia C, Tang L, Hou C (2023) Herbal formula Jiawei Xiaochengqi decoction prevents postoperative abdominal adhesion in a rat model through inhibition of CXCL2-CXCR2 pathway. Phytomedicine 111:154662
Liu B, Zhang Q, Wu X, Fu Y, Wang H, Guan Y, Yang S, Liu Y, Cao W, Wang J (2019) Effect of Bletilla striata on the prevention of postoperative peritoneal adhesions in abrasion-induced rat model. eCAM 2019
Liu H, Xu H, Sun H, Xu H, Han J, Zhao L, Li X, Sun X, Dong X, Xu R (2023a) Tetrahydroberberrubine prevents peritoneal adhesion by suppressing inflammation and extracellular matrix accumulation. Eur J Pharmacol. 175803
Mahmoudieh M, Keleidari B, Esfahani FN, Zolfaghari B, Melali H, Jazi AHD, Mehdinezhad N, Mokhtari M (2020) The effect of Punica granatum L. flower extract on post-surgical peritoneal adhesions in a rat model. Eur J Obstet Gynecol Reprod Biol 246:113–116
Mohamed ME, Abduldaium YS, Younis NS (2020) Ameliorative effect of linalool in cisplatin-induced nephrotoxicity: the role of HMGB1/TLR4/NF-κB and Nrf2/HO1 pathways. Biomolecules 10:1488
Nair SK, Bhat IK, Aurora AL (1974) Role of proteolytic enzyme in the prevention of postoperative intraperitoneal adhesions. Arch Surg 108:849–853
Parsaei P, Karimi M, Asadi SY, Rafieian-Kopaei M (2013) Bioactive components and preventive effect of green tea (Camellia sinensis) extract on post-laparotomy intra-abdominal adhesion in rats. Int Surg J 11:811–815
Peana AT, D’Aquila PS, Panin F, Serra G, Pippia P, Moretti MDL (2002) Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomedicine 9:721–726
Pereira I, Severino P, Santos AC, Silva AM, Souto EB (2018) Linalool bioactive properties and potential applicability in drug delivery systems. Colloids Surf B 171:566–578
Rahimi VB, Shirazinia R, Fereydouni N, Zamani P, Darroudi S, Sahebkar AH, Askari VR (2017) Comparison of honey and dextrose solution on post-operative peritoneal adhesion in rat model. Biomed Pharmacother 92:849–855
Raisi A, Dezfoulian O, Davoodi F, Taheri S, Ghahremani SA (2021) Salvia miltiorrhiza hydroalcoholic extract inhibits postoperative peritoneal adhesions in rats. BMC Complement Med Ther 21:1–11
Rakhshandeh H, Baradaran Rahimi V, Habibi Z, Sirousi Z, Askari VR (2022) Punica granatum seed oil detracts peritoneal adhesion: perusing antioxidant, anti-inflammatory, antifibrotic, and antiangiogenic impacts. Physiol. Rep 10:e15545
Schanaider A, Cotta-Pereira R, Silva PC, Macedo-Ramos H, Silva JD, Teixeira PA, Pannain VL, Rocco PR, Baetas-da-Cruz W (2016) Exogenous pulmonary surfactant prevents the development of intra-abdominal adhesions in rats. J Cell Mol Med 20:632–643
Schnüriger B, Barmparas G, Branco BC, Lustenberger T, Inaba K, Demetriades D (2011) Prevention of postoperative peritoneal adhesions: a review of the literature. Am J Surg 201:111–121
Sheu C, Shalumon K, Chen C-H, Kuo C-Y, Fong YT, Chen J-P (2016) Dual crosslinked hyaluronic acid nanofibrous membranes for prolonged prevention of post-surgical peritoneal adhesion. J Mater Chem B 4:6680–6693
Shi M, Liu H, Zhang T, Zhang M, Tang X, Zhang Z, Lu W, Yang S, Jiang Z, Cui Q (2022) Extracellular vesicles derived from adipose mesenchymal stem cells promote peritoneal healing by activating MAPK-ERK1/2 and PI3K-Akt to alleviate postoperative abdominal adhesion. Stem Cells Int 2022
Sudirman T, Hatta M, Prihantono P, Bukhari A, Tedjasaputra TR, Lie H (2022) Vitamin E administration as preventive measures for peritoneal/intra-abdominal adhesions: a systematic review and meta-analysis. Ann. Surg: 104225
Süntar I, Demirel MA, Ceribasi AO, Ergin I, Gökbulut A (2021) Preventive effect of Rumex crispus L. on surgically induced intra-abdominal adhesion model in rats. DARU J Pharm Sci 29:101–115
Wei G, Chen X, Wang G, Fan L, Wang K, Li X (2016) Effect of resveratrol on the prevention of intra-abdominal adhesion formation in a rat model. Cell Physiol Biochem 39:33–46
Wu Y, Duan X, Gao Z, Yang N, Xue F (2022) AICAR attenuates postoperative abdominal adhesion formation by inhibiting oxidative stress and promoting mesothelial cell repair. Plos One 17:e0272928
Wu F, Liu W, Feng H, Long L, Hou L, Hou C (2020) Application of traditional Chinese medicines in postoperative abdominal adhesion. eCAM 2020
Zhang H, Song Y, Li Z, Zhang T, Zeng L (2016) Evaluation of breviscapine on prevention of experimentally induced abdominal adhesions in rats. Am J Surg 211:1143–1152
Zhao J-M, Jin Z-Z, Zhao Q-Z (2017) The preventive effect of ambroxol hydrochloride chitosan on postoperative intraperitoneal adhesion formation in a rat model. Acta Chir Belg 117:232–237
Acknowledgements
The present study was extracted from the DVSc thesis of Farshid Davoodi conducted at Urmia University.
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This work was supported by the Vice Chancellor of Research and Technology of Urmia University.
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Farshid Davoodi: investigation, methodology, conceptualization, writing—original draft, formal analysis, conceptualization. Saeed Azizi: project administration, methodology, conceptualization, supervision, writing—review and editing. Safiyeh Aghazadeh: methodology, visualization, conceptualization, writing—review and editing. Omid Dezfoulian: investigation, conceptualization, data curation, writing—review and editing, validation. The authors declare that all data were generated in-house and that no paper mill was used.
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Davoodi, F., Azizi, S., Aghazadeh, S. et al. Effects of linalool on postoperative peritoneal adhesions in rats. Naunyn-Schmiedeberg's Arch Pharmacol 397, 5145–5155 (2024). https://doi.org/10.1007/s00210-024-02943-w
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DOI: https://doi.org/10.1007/s00210-024-02943-w