Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats.
Apoptosis
Chitosan
Cytokines
Matrix metalloproteinases
Oral mucositis
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
17
11
2021
accepted:
17
01
2022
pubmed:
23
1
2022
medline:
1
4
2022
entrez:
22
1
2022
Statut:
ppublish
Résumé
Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group. It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.
Sections du résumé
BACKGROUND
BACKGROUND
Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX.
METHODS AND RESULTS
RESULTS
Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group.
CONCLUSION
CONCLUSIONS
It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.
Identifiants
pubmed: 35064410
doi: 10.1007/s11033-022-07158-x
pii: 10.1007/s11033-022-07158-x
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Chitosan
9012-76-4
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3237-3245Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Harris DJ (2006) Cancer treatment-induced mucositis pain: strategies for assessment and management. Ther Clin Risk Manag 2:251–258. https://doi.org/10.2147/TCRM.2006.2.3.251
doi: 10.2147/TCRM.2006.2.3.251
pubmed: 18360600
pmcid: 1936261
Al-Ansari S, Zecha JAEM, Barasch A et al (2015) Oral Mucositis Induced By Anticancer Therapies. Curr Oral Health Rep 2:202–211. https://doi.org/10.1007/S40496-015-0069-4
doi: 10.1007/S40496-015-0069-4
pubmed: 26523246
pmcid: 4623065
Cinausero M, Aprile G, Ermacora P et al (2017) New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury. Front Pharmacol 8:354. https://doi.org/10.3389/FPHAR.2017.00354
doi: 10.3389/FPHAR.2017.00354
pubmed: 28642709
pmcid: 5462992
Cawley MM, Benson LM (2005) Current trends in managing oral mucositis. Clin J Oncol Nurs 9:584–592. https://doi.org/10.1188/05.CJON.584-592
doi: 10.1188/05.CJON.584-592
pubmed: 16235585
Munaretto JC, Ponzoni D, Sabbagh-Haddad A, Puricelli E (2011) Preliminary histological analysis of methotrexate-induced oral mucositis: experimental study in mice. Revista da Faculdade de Odontologia – UPF 16:144–148. https://doi.org/10.5335/RFO.V16I2.2118
doi: 10.5335/RFO.V16I2.2118
Alrifai A, Kamal A (2019) Protective role of honey on the dorsal surface of the tongue of chemotherapy treated albino rats (immunohistochemical study). https://www.researchgate.net/publication/332979098
Barbosa F, Tanus-Santos JE, Gerlach RF, Parsons PJ (2005) A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs. Environ Health Perspect 113:1669–1674. https://doi.org/10.1289/EHP.7917
doi: 10.1289/EHP.7917
pubmed: 16330345
pmcid: 1314903
Komousani KA, Moselhy SS (2011) Modulation of lead biohazards using a combination of epicatechin and lycopene in rats. Hum Exp Toxicol 30:1674–1681. https://doi.org/10.1177/0960327110396536
doi: 10.1177/0960327110396536
pubmed: 21262865
Wang Z, Yan Y, Yu X et al (2016) Protective effects of chitosan and its water-soluble derivatives against lead-induced oxidative stress in mice. Int J Biol Macromol 83:442–449. https://doi.org/10.1016/J.IJBIOMAC.2015.10.017
doi: 10.1016/J.IJBIOMAC.2015.10.017
pubmed: 26454108
Mutlu N, Ersan Y, Nur G, Koç E (2009) Protective effect of caffeic acid phenethyl ester against lead acetate-induced hepatotoxicity in mice. Kafkas Üniversitesi Veteriner Fakültesi Dergisi 17. https://doi.org/10.9775/KVFD.2010.2717
Yeoh ASJ, Gibson RJ, Yeoh EEK et al (2007) A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-κB, COX-1, and COX-2. Mol Cancer Ther 6:2319–2327. https://doi.org/10.1158/1535-7163.MCT-07-0113
doi: 10.1158/1535-7163.MCT-07-0113
pubmed: 17699727
Bowen JM, Gibson RJ, Tsykin A et al (2007) Gene expression analysis of multiple gastrointestinal regions reveals activation of common cell regulatory pathways following cytotoxic chemotherapy. Int J Cancer 121:1847–1856. https://doi.org/10.1002/IJC.22895
doi: 10.1002/IJC.22895
pubmed: 17594691
Al-Dasooqi N, Sonis ST, Bowen JM et al (2013) Emerging evidence on the pathobiology of mucositis. Support Care Cancer 21:2075–2083. https://doi.org/10.1007/S00520-013-1810-Y
doi: 10.1007/S00520-013-1810-Y
pubmed: 23604521
Bowen J, Al-Dasooqi N, Bossi P et al (2019) The pathogenesis of mucositis: updated perspectives and emerging targets. Support Care Cancer 27:4023–4033. https://doi.org/10.1007/S00520-019-04893-Z
doi: 10.1007/S00520-019-04893-Z
pubmed: 31286231
Al-Azri AR, Gibson RJ, Keefe DMK, Logan RM (2013) Matrix metalloproteinases: do they play a role in mucosal pathology of the oral cavity? Oral Dis 19:347–359. https://doi.org/10.1111/ODI.12023
doi: 10.1111/ODI.12023
pubmed: 23033841
Rajagopalan PTR, Zhang Z, McCourt L et al (2002) Interaction of dihydrofolate reductase with methotrexate: ensemble and single-molecule kinetics. Proc Natl Acad Sci USA 99:13481–13486. https://doi.org/10.1073/PNAS.172501499
doi: 10.1073/PNAS.172501499
pubmed: 12359872
pmcid: 129699
Peterson DE, Lalla RV (2010) Oral mucositis: the new paradigms. Curr Opin Oncol 22:318–322. https://doi.org/10.1097/CCO.0B013E32833A9FAB
doi: 10.1097/CCO.0B013E32833A9FAB
pubmed: 20485169
pmcid: 20485169
Ahmed AAM, Selim MAA, El-Sayed NM (2017) α-Lipoic acid ameliorates oral mucositis and oxidative stress induced by methotrexate in rats. Histological and immunohistochemical study. Life Sci 171:51–59. https://doi.org/10.1016/J.LFS.2017.01.001
doi: 10.1016/J.LFS.2017.01.001
pubmed: 28062278
Khanal L, Yadav P, Baral P et al (2019) Effect of local bee honey on dihydrofolate reductase enzyme inhibitor-induced mucositis: a histological study on albino Wistar rats. Indian J Dent Res 30:708–715. https://doi.org/10.4103/IJDR.IJDR_689_17
doi: 10.4103/IJDR.IJDR_689_17
pubmed: 31854361
Ozcicek F, Kara AV, Akbas EM et al (2020) Effects of anakinra on the small intestine mucositis induced by methotrexate in rats. Exp Anim 69:144–152. https://doi.org/10.1538/EXPANIM.19-0057
doi: 10.1538/EXPANIM.19-0057
pubmed: 31787709
Kim SG, Chae CH, Cho BO et al (2006) Apoptosis of oral epithelial cells in oral lichen planus caused by upregulation of BMP-4. J Oral Pathol Med 35:37–45. https://doi.org/10.1111/J.1600-0714.2005.00373.X
doi: 10.1111/J.1600-0714.2005.00373.X
pubmed: 16393252
Mannello F, Luchetti F, Falcieri E, Papa S (2005) Multiple roles of matrix metalloproteinases during apoptosis. Apoptosis 10:19–24. https://doi.org/10.1007/S10495-005-6058-7
doi: 10.1007/S10495-005-6058-7
pubmed: 15711919
van der Beek JN, Oosterom N, Pieters R et al (2019) The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: a systematic review. Crit Rev Oncol Hematol 142:1–8. https://doi.org/10.1016/J.CRITREVONC.2019.07.003
doi: 10.1016/J.CRITREVONC.2019.07.003
pubmed: 31323533
Toz H, Değer Y (2018) The effect of chitosan on the erythrocyte antioxidant potential of lead toxicity-induced rats. Biol Trace Elem Res 184:114–118. https://doi.org/10.1007/S12011-017-1164-2
doi: 10.1007/S12011-017-1164-2
pubmed: 28971372
Wu KY, Wu M, Fu ML et al (2006) A novel chitosan CpG nanoparticle regulates cellular and humoral immunity of mice. Biomed Environ Sci 19:87–95
pubmed: 16827178
Saravanakumar K, Mariadoss AVA, Sathiyaseelan A et al (2021) pH-sensitive release of fungal metabolites from chitosan nanoparticles for effective cytotoxicity in prostate cancer (PC3) cells. Process Biochem 102:165–172. https://doi.org/10.1016/J.PROCBIO.2020.12.005
doi: 10.1016/J.PROCBIO.2020.12.005
Mariadoss AVA, Vinayagam R, Senthilkumar V et al (2019) Phloretin loaded chitosan nanoparticles augments the pH-dependent mitochondrial-mediated intrinsic apoptosis in human oral cancer cells. Int J Biol Macromol 130:997–1008. https://doi.org/10.1016/J.IJBIOMAC.2019.03.031
doi: 10.1016/J.IJBIOMAC.2019.03.031
pubmed: 30844461
Farraj T, Ajam M, Gençosman S et al (2021) Biochemical significance of biomaterials based on the chitin-chitosan axis. Acta Sci Gastron Disord 4. https://www.issn.org/2582-1091
Şenel S, Kremer MJ, Kaş S et al (2000) Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials 21:2067–2071. https://doi.org/10.1016/S0142-9612(00)00134-4
doi: 10.1016/S0142-9612(00)00134-4
pubmed: 10966016
Patel A, Rajesh S, Chandrashekhar VM et al (2013) A rat model against chemotherapy plus radiation-induced oral mucositis. Saudi Pharm J 21:399–403. https://doi.org/10.1016/J.JSPS.2012.11.003
doi: 10.1016/J.JSPS.2012.11.003
pubmed: 24227960
pmcid: 3824950
Sehirli A, Aksoy U, Kermeoglu F et al (2019) Protective effect of alpha-lipoic acid against apical periodontitis-induced cardiac injury in rats. Eur J Oral Sci 127:333–339. https://doi.org/10.1111/EOS.12618
doi: 10.1111/EOS.12618
pubmed: 30995351
Sathiyaseelan A, Saravanakumar K, Mariadoss AVA, Wang MH (2021) pH-controlled nucleolin targeted release of dual drug from chitosan-gold based aptamer functionalized nano drug delivery system for improved glioblastoma treatment. Carbohyd Polym 262. https://doi.org/10.1016/J.CARBPOL.2021.117907
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275. https://doi.org/10.1016/s0021-9258(19)52451-6
doi: 10.1016/s0021-9258(19)52451-6
Vissink A, Jansma J, Spijkervet FKL et al (2003) Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med 14:199–212. https://doi.org/10.1177/154411130301400305
doi: 10.1177/154411130301400305
pubmed: 12799323
pmcid: 12799323
Çakir T, Polat C, Baştürk A et al (2015) The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. Eur Rev Med Pharmacol Sci 19:2132–2139
pubmed: 26125279
Kuduban O, Mazlumoglu MR, Kuduban SD et al (2016) The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate. J Appl Oral Sci 24:423–430. https://doi.org/10.1590/1678-775720160139
doi: 10.1590/1678-775720160139
pubmed: 27812611
pmcid: 5083018
Jhundoo HD, Siefen T, Liang A et al (2020) Anti-inflammatory activity of chitosan and 5-amino salicylic acid combinations in experimental colitis. Pharmaceutics 12:1–16. https://doi.org/10.3390/PHARMACEUTICS12111038
doi: 10.3390/PHARMACEUTICS12111038
Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174. https://doi.org/10.1038/NRC745
doi: 10.1038/NRC745
pubmed: 11990853
Frisch SM, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626. https://doi.org/10.1083/jcb.124.4.619
doi: 10.1083/jcb.124.4.619
pubmed: 8106557
Bergers G, Coussens LM (2000) Extrinsic regulators of epithelial tumor progression: metalloproteinases. Curr Opin Genet Dev 10:120–127. https://doi.org/10.1016/S0959-437X(99)00043-X
doi: 10.1016/S0959-437X(99)00043-X
pubmed: 10679388
Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123–2133. https://doi.org/10.1101/gad.815400
doi: 10.1101/gad.815400
pubmed: 10970876
Häyrinen-Immonen R, Sorsa T, Nordström D et al (1993) Collagenase and stromelysin in recurrent aphthous ulcers (RAU). Int J Oral Maxillofac Surg 22:46–49. https://doi.org/10.1016/S0901-5027(05)80357-1
doi: 10.1016/S0901-5027(05)80357-1
pubmed: 8459124
Mazzarella N, Femiano F, Gombos F et al (2006) Matrix metalloproteinase gene expression in oral lichen planus: erosive vs. reticular forms. J Eur Acad Dermatol Venereol 20:953–957. https://doi.org/10.1111/j.1468-3083.2006.01693.x
doi: 10.1111/j.1468-3083.2006.01693.x
pubmed: 16922944
Said S, Golitz L (2011) Vesiculobullous eruptions of the oral cavity. Otolaryngol Clin North Am 44:133–160. https://doi.org/10.1016/J.OTC.2010.09.005
doi: 10.1016/J.OTC.2010.09.005
pubmed: 21093627
Worswick S, Cotliar J (2011) Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options. Dermatol Ther 24:207–218. https://doi.org/10.1111/J.1529-8019.2011.01396.X
doi: 10.1111/J.1529-8019.2011.01396.X
pubmed: 21410610
Mariadoss AVA, Saravanakumar K, Sathiyaseelan A et al (2021) Smart drug delivery of p-Coumaric acid loaded aptamer conjugated starch nanoparticles for effective triple-negative breast cancer therapy. Int J Biol Macromol 195:22–29. https://doi.org/10.1016/J.IJBIOMAC.2021.11.170
doi: 10.1016/J.IJBIOMAC.2021.11.170
pubmed: 34861273
Abo-Haded HM, Elkablawy MA, Al-Johani Z et al (2017) Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity. PLoS One 12. https://doi.org/10.1371/JOURNAL.PONE.0174295
Helal MG, Said E (2020) Tranilast attenuates methotrexate-induced renal and hepatic toxicities: role of apoptosis-induced tissue proliferation. J Biochem Mol Toxicol 34. https://doi.org/10.1002/JBT.22466