Research Article
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The Therapeutic Effect of p-Coumaric Acid on Lung Toxicity Induced by Methotrexate in Rats

Year 2024, Volume: 3 Issue: 2, 57 - 62, 30.06.2024
https://doi.org/10.59518/farabimedj.1484155

Abstract

The use of methotrexate (MTX), a chemotherapy agent, is limited by a number of side effects, including pulmonary toxicity. Oxidative stress (OS) and inflammation are possible mechanisms of MTX-associated pulmonary toxicity. p-Coumaric acid (PCA) is a phenolic acid that has been demonstrated to exert a number of beneficial effects on human health, particularly in relation to antioxidant and anti-inflammatory activity. The potential effects of PCA in reducing MTX-induced pulmonary toxicity were investigated in the current study. After MTX (20 mg/kg) was administered to the rats on day 1, two different doses of PCA (2 and 4 mg/kg) were administered intraperitoneally for 3 days and the levels of OS, inflammation and apoptosis were assessed in the lung tissues collected on day 5. PCA applications largely eliminated MTX-induced OS, inflammation and apoptosis in lung tissue via enhancing the capacity of endogenous antioxidant system. The therapeutic effect of PCA against MTX-induced pulmonary toxicity should be re-evaluated in more systematic studies.

Ethical Statement

This study was approved by the Local Animal Research Ethics Committee of Karadeniz Technical University (Protocol no: 2023/06) and performed according to the animal research reporting of in vivo experiments (ARRIVE) guidelines.

Thanks

The authors wish to thank Sait Al and Ibrahim Aydin from Surgical Practice and Research Center of Karadeniz Technical University for professional assistance with the experimental studies.

References

  • Patel NN, Ghodasara DJ, Pandey S, et al. Subacute toxicopathological studies of methotrexate in Wistar rats. Veterinary World. 2014;7(7):489-495.
  • Hamed KM, Dighriri IM, Baomar AF, et al. Overview of methotrexate toxicity: A Comprehensive literature review. Cureus. 2022;14(9):e29518. doi:10.7759/cureus.29518
  • Gaies E, Jebabli N, Trabelsi S, et al. Methotrexate side effects: Review article. J Drug Metab Toxicol. 2012;3:4. doi:10.4172/2157-7609.1000125
  • Ohbayashi M, Suzuki M, Yashiro Y, et al. Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro. J Toxicol Sci. 2010;35(5):653-661. doi:10.2131/jts.35.653
  • Zaki SM, Hussein GHA, Khalil HMA, Abd Algaleel WA. Febuxostat ameliorates methotrexate-induced lung damage. Folia Morphol (Warsz). 2021;80(2):392-402. doi:10.5603/FM.a2020.0075
  • Althagafy HS, Sharawi ZW, Batawi AH, et al. Buspirone attenuated methotrexate-induced hippocampal toxicity in rats by regulating Nrf2/HO-1, PPAR-γ, NF-κB/nNOS, and ROS/NLRP3/caspase-1 signaling pathways. J Biochem Mol Toxicol. 2023;37(9):e23414. doi:10.1002/jbt.23414
  • Katturajan R, Vijayalakshmi S, Rasool M, Evan Prince S. Molecular toxicity of methotrexate in rheumatoid arthritis treatment: A novel perspective and therapeutic implications. Toxicology. 2021;461:152909. doi:10.1016/j.tox.2021.152909
  • Arpag H, Gül M, Aydemir Y, et al. Protective effects of alpha-lipoic acid on methotrexate-induced oxidative lung injury in rats. J Invest Surg. 2018;31(2):107-113. doi:10.1080/08941939.2017.1296513
  • Mohamed DI, Khairy E, Tawfek SS, Habib EK, Fetouh MA. Coenzyme Q10 attenuates lung and liver fibrosis via modulation of autophagy in methotrexate treated rat. Biomed Pharmacother. 2019;109:892-901. doi:10.1016/j.biopha.2018.10.133
  • Bedoui Y, Guillot X, Sélambarom J, et al. Methotrexate an old drug with new tricks. Int J Mol Sci. 2019;20(20):5023. doi:10.3390/ijms20205023
  • Alamir I, Boukhettala N, Aziz M, Breuillé D, Déchelotte P, Coëffier M. Beneficial effects of cathepsin inhibition to prevent chemotherapy-induced intestinal mucositis. Clin Exp Immunol. 2010;162(2):298-305. doi:10.1111/j.1365-2249.2010.04220.x
  • Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-1167. doi:10.1089/ars.2012.5149
  • Mammadov R, Suleyman B, Akturan S, et al. Effect of lutein on methotrexate-induced oxidative lung damage in rats: biochemical and histopathological assessment. Korean J Intern Med. 2019;34:1279-1286. doi:10.3904/kjim.2018.145
  • Tanaka T, Aoki R, Terasaki M. Potential chemopreventive effects of dietary combination of phytochemicals against cancer development. Pharmaceuticals (Basel). 2023;16(11):1591. doi:10.3390/ph16111591
  • Tehami W, Nani A, Khan NA, Hichami A. New insights into the anticancer effects of p-coumaric acid: Focus on colorectal cancer. Dose Response. 2023;21(1):15593258221150704. doi:10.1177/15593258221150704
  • Pei K, Ou J, Huang J, Ou S. p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities. J Sci Food Agric. 2016;96(9):2952-2962. doi:10.1002/jsfa.7578
  • Ekinci-Akdemir FN, Albayrak M, Calik M, Bayir Y, Gulcin I. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines. 2017;5:18. doi:10.3390/biomedicines5020018
  • Ayazoglu Demir E, Mentese A, Kucuk H, Alemdar NT, Demir S. p-Coumaric acid alleviates cisplatin-induced ovarian toxicity in rats. J Obstet Gynaecol Res. 2022;48(2):411-419. doi:10.1111/jog.15119
  • Abdel-Wahab MH, El-Mahdy MA, Abd-Ellah MF, Helal GK, Khalifa F, Hamada FMA. Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart. Pharmacol Res. 2003;48(5):461-465. doi:10.1016/s1043-6618(03)00214-7
  • Rafiee Z, Moaiedi MZ, Gorji AV, Mansouri E. p-Coumaric acid mitigates doxorubicin-induced nephrotoxicity through suppression of oxidative stress, inflammation and apoptosis. Arch Med Res. 2020;51:32-40. doi:10.1016/j.arcmed.2019.12.004
  • Erboga M, Aktas C, Erboga ZF, Donmez YB, Gurel A. Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats. Ren Fail. 2015;37(9):1492-1497. doi:10.3109/0886022X.2015.1074521
  • Yuksel Y, Yuksel R, Yagmurca M, et al. Effects of quercetin on methotrexate-induced nephrotoxicity in rats. Hum Exp Toxicol. 2017;36(1):51-61. doi:10.1177/0960327116637414
  • Sultana S. Protective effect of baicalin on methotrexate-induced mitochondrial damage in testicular tissues of rats. J King Saud Univ Sci. 2022;34:102343. doi:10.1016/j.jksus.2022.102343
  • Ekinci-Akdemir FN, Gozeler MS, Yildirim S, Kiziltunc A, Eser G, Askin S. The protective effect of coumaric acid against cisplatin-induced ototoxicity in rats. Med Science. 2018;7(2):373-377. doi:10.5455/medscience.2018.07.8779
  • Prince PSM, Roy AJ. p-Coumaric acid attenuates apoptosis in isoproterenol-induced myocardial infarcted rats by inhibiting oxidative stress. Int J Cardiol. 2013;168(4):3259-3266. doi:10.1016/j.ijcard.2013.04.138
  • Smith PK, Krohn RI, Hermanson GT, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85. doi:10.1016/0003-2697(85)90442-7
  • Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-278. doi:10.1016/0003-2697(78)90342-1
  • Demir S, Mentese A, Livaoglu A, Demir EA, Alemdar NT, Aliyazicioglu Y. Therapeutic effect of sinapic acid against 5-fluorouracil-induced oxidative stress and inflammation in rat ovarium: An experimental approach. Farabi Med J. 2023;2(2):1-7. doi:10.59518/farabimedj.1221397
  • Kurt A, Tumkaya L, Turut H, et al. Protective effects of infliximab on lung injury induced by methotrexate. Arch Bronconeumol. 2015;51(11):551-557. doi:10.1016/j.arbres.2015.03.018
  • Shen Y, Song X, Li L, et al. Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation. Biomed Pharmacother. 2019;111:579-587. doi:10.1016/j.biopha.2018.12.074
  • Demir S, Kazaz IO, Kerimoglu G, et al. Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress. Rev Int Androl. 2024;22(1):1-7. doi:10.22514/j.androl.2024.001
  • Ayazoglu Demir E, Mentese A, Kucuk H, Turkmen Alemdar N, Demir S. The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats. J Biochem Mol Toxicol. 2023;37(9):e23408. doi:10.1002/jbt.23408
  • Kahraman H, Kurutaş E, Tokur M, et al. Protective effects of erythropoietin and N-acetylcysteine on methotrexate-induced lung injury in rats. Balkan Med J. 2013;30(1):99-104. doi:10.5152/balkanmedj.2012.078
  • Kalemci S, Dirican N, Cetin ES, et al. The efficacy of minocycline against methotrexate-induced pulmonary fibrosis in mice. Eur Rev Med Pharmacol Sci. 2013;17(24):3334-3340.
  • Shiromwar SS, Chidrawar VR. Combined effects of p-coumaric acid and naringenin against doxorubicin-induced cardiotoxicity in rats. Phcog Res. 2011;3:214-219. doi:10.4103/0974-8490.85012
  • Sabitha R, Nishi K, Gunasekaran VP, et al. p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models. Chem Biol Interact. 2020;321:109044. doi:10.1016/j.cbi.2020.109044
  • Ali YA, Ahmed AAE, Abd El-Raouf OM, Elkhoely A, Gad AM. Polydatin combats methotrexate-induced pulmonary fibrosis in rats: Involvement of biochemical and histopathological assessment. J Biochem Mol Toxicol. 2022;36(5):e23019. doi:10.1002/jbt.23019
  • Taha MME, Mohan S, Khediash H, et al. Amelioration of carbon tetrachloride-induced liver injury by p-coumaric acid. Curr Top Nutraceutical Res. 2020;18(4):1-6. doi:10.37290/ctnr2641-452X.18:1-6

Sıçanlarda Metotreksatın Neden Olduğu Akciğer Toksisitesi Üzerine p-Kumarik Asidin Terapötik Etkisi

Year 2024, Volume: 3 Issue: 2, 57 - 62, 30.06.2024
https://doi.org/10.59518/farabimedj.1484155

Abstract

Bir kemoterapötik ajan olarak metotreksatın (MTX) kullanımı, akciğer toksisitesi de dahil olmak üzere bir takım yan etkiler nedeniyle sınırlıdır. Oksidatif stres (OS) ve inflamasyon, MTX ile ilişkili akciğer toksisitesinin olası mekanizmalarıdır. p-Kumarik asit (PCA), özellikle antioksidan ve anti-inflamatuar olmak üzere insan sağlığı üzerinde çeşitli yararlı etkileri olan bir fenolik asittir. Bu çalışmada PCA'nın MTX kaynaklı akciğer toksisitesini azaltmadaki potansiyel etkileri araştırıldı. Ratlara 1. günde MTX (20 mg/kg) enjeksiyonunu takiben 3 gün boyunca iki farklı dozda PCA (2 ve 4 mg/kg) intraperitoneal olarak uygulandıktan sonra 5.günde akciğer dokuları toplanarak OS, inflamasyon ve apoptoz düzeyleri değerlendirildi. PCA uygulamaları, endojen antioksidan sistemin kapasitesini artırarak akciğer dokusunda MTX'in neden olduğu OS, inflamasyon ve apoptozu büyük ölçüde ortadan kaldırdı. PCA'nın MTX kaynaklı akciğer toksisitesine karşı terapötik etkisinin daha sistematik çalışmalarla yeniden değerlendirilmesi gerekmektedir.

References

  • Patel NN, Ghodasara DJ, Pandey S, et al. Subacute toxicopathological studies of methotrexate in Wistar rats. Veterinary World. 2014;7(7):489-495.
  • Hamed KM, Dighriri IM, Baomar AF, et al. Overview of methotrexate toxicity: A Comprehensive literature review. Cureus. 2022;14(9):e29518. doi:10.7759/cureus.29518
  • Gaies E, Jebabli N, Trabelsi S, et al. Methotrexate side effects: Review article. J Drug Metab Toxicol. 2012;3:4. doi:10.4172/2157-7609.1000125
  • Ohbayashi M, Suzuki M, Yashiro Y, et al. Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro. J Toxicol Sci. 2010;35(5):653-661. doi:10.2131/jts.35.653
  • Zaki SM, Hussein GHA, Khalil HMA, Abd Algaleel WA. Febuxostat ameliorates methotrexate-induced lung damage. Folia Morphol (Warsz). 2021;80(2):392-402. doi:10.5603/FM.a2020.0075
  • Althagafy HS, Sharawi ZW, Batawi AH, et al. Buspirone attenuated methotrexate-induced hippocampal toxicity in rats by regulating Nrf2/HO-1, PPAR-γ, NF-κB/nNOS, and ROS/NLRP3/caspase-1 signaling pathways. J Biochem Mol Toxicol. 2023;37(9):e23414. doi:10.1002/jbt.23414
  • Katturajan R, Vijayalakshmi S, Rasool M, Evan Prince S. Molecular toxicity of methotrexate in rheumatoid arthritis treatment: A novel perspective and therapeutic implications. Toxicology. 2021;461:152909. doi:10.1016/j.tox.2021.152909
  • Arpag H, Gül M, Aydemir Y, et al. Protective effects of alpha-lipoic acid on methotrexate-induced oxidative lung injury in rats. J Invest Surg. 2018;31(2):107-113. doi:10.1080/08941939.2017.1296513
  • Mohamed DI, Khairy E, Tawfek SS, Habib EK, Fetouh MA. Coenzyme Q10 attenuates lung and liver fibrosis via modulation of autophagy in methotrexate treated rat. Biomed Pharmacother. 2019;109:892-901. doi:10.1016/j.biopha.2018.10.133
  • Bedoui Y, Guillot X, Sélambarom J, et al. Methotrexate an old drug with new tricks. Int J Mol Sci. 2019;20(20):5023. doi:10.3390/ijms20205023
  • Alamir I, Boukhettala N, Aziz M, Breuillé D, Déchelotte P, Coëffier M. Beneficial effects of cathepsin inhibition to prevent chemotherapy-induced intestinal mucositis. Clin Exp Immunol. 2010;162(2):298-305. doi:10.1111/j.1365-2249.2010.04220.x
  • Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-1167. doi:10.1089/ars.2012.5149
  • Mammadov R, Suleyman B, Akturan S, et al. Effect of lutein on methotrexate-induced oxidative lung damage in rats: biochemical and histopathological assessment. Korean J Intern Med. 2019;34:1279-1286. doi:10.3904/kjim.2018.145
  • Tanaka T, Aoki R, Terasaki M. Potential chemopreventive effects of dietary combination of phytochemicals against cancer development. Pharmaceuticals (Basel). 2023;16(11):1591. doi:10.3390/ph16111591
  • Tehami W, Nani A, Khan NA, Hichami A. New insights into the anticancer effects of p-coumaric acid: Focus on colorectal cancer. Dose Response. 2023;21(1):15593258221150704. doi:10.1177/15593258221150704
  • Pei K, Ou J, Huang J, Ou S. p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities. J Sci Food Agric. 2016;96(9):2952-2962. doi:10.1002/jsfa.7578
  • Ekinci-Akdemir FN, Albayrak M, Calik M, Bayir Y, Gulcin I. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines. 2017;5:18. doi:10.3390/biomedicines5020018
  • Ayazoglu Demir E, Mentese A, Kucuk H, Alemdar NT, Demir S. p-Coumaric acid alleviates cisplatin-induced ovarian toxicity in rats. J Obstet Gynaecol Res. 2022;48(2):411-419. doi:10.1111/jog.15119
  • Abdel-Wahab MH, El-Mahdy MA, Abd-Ellah MF, Helal GK, Khalifa F, Hamada FMA. Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart. Pharmacol Res. 2003;48(5):461-465. doi:10.1016/s1043-6618(03)00214-7
  • Rafiee Z, Moaiedi MZ, Gorji AV, Mansouri E. p-Coumaric acid mitigates doxorubicin-induced nephrotoxicity through suppression of oxidative stress, inflammation and apoptosis. Arch Med Res. 2020;51:32-40. doi:10.1016/j.arcmed.2019.12.004
  • Erboga M, Aktas C, Erboga ZF, Donmez YB, Gurel A. Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats. Ren Fail. 2015;37(9):1492-1497. doi:10.3109/0886022X.2015.1074521
  • Yuksel Y, Yuksel R, Yagmurca M, et al. Effects of quercetin on methotrexate-induced nephrotoxicity in rats. Hum Exp Toxicol. 2017;36(1):51-61. doi:10.1177/0960327116637414
  • Sultana S. Protective effect of baicalin on methotrexate-induced mitochondrial damage in testicular tissues of rats. J King Saud Univ Sci. 2022;34:102343. doi:10.1016/j.jksus.2022.102343
  • Ekinci-Akdemir FN, Gozeler MS, Yildirim S, Kiziltunc A, Eser G, Askin S. The protective effect of coumaric acid against cisplatin-induced ototoxicity in rats. Med Science. 2018;7(2):373-377. doi:10.5455/medscience.2018.07.8779
  • Prince PSM, Roy AJ. p-Coumaric acid attenuates apoptosis in isoproterenol-induced myocardial infarcted rats by inhibiting oxidative stress. Int J Cardiol. 2013;168(4):3259-3266. doi:10.1016/j.ijcard.2013.04.138
  • Smith PK, Krohn RI, Hermanson GT, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85. doi:10.1016/0003-2697(85)90442-7
  • Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-278. doi:10.1016/0003-2697(78)90342-1
  • Demir S, Mentese A, Livaoglu A, Demir EA, Alemdar NT, Aliyazicioglu Y. Therapeutic effect of sinapic acid against 5-fluorouracil-induced oxidative stress and inflammation in rat ovarium: An experimental approach. Farabi Med J. 2023;2(2):1-7. doi:10.59518/farabimedj.1221397
  • Kurt A, Tumkaya L, Turut H, et al. Protective effects of infliximab on lung injury induced by methotrexate. Arch Bronconeumol. 2015;51(11):551-557. doi:10.1016/j.arbres.2015.03.018
  • Shen Y, Song X, Li L, et al. Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation. Biomed Pharmacother. 2019;111:579-587. doi:10.1016/j.biopha.2018.12.074
  • Demir S, Kazaz IO, Kerimoglu G, et al. Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress. Rev Int Androl. 2024;22(1):1-7. doi:10.22514/j.androl.2024.001
  • Ayazoglu Demir E, Mentese A, Kucuk H, Turkmen Alemdar N, Demir S. The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats. J Biochem Mol Toxicol. 2023;37(9):e23408. doi:10.1002/jbt.23408
  • Kahraman H, Kurutaş E, Tokur M, et al. Protective effects of erythropoietin and N-acetylcysteine on methotrexate-induced lung injury in rats. Balkan Med J. 2013;30(1):99-104. doi:10.5152/balkanmedj.2012.078
  • Kalemci S, Dirican N, Cetin ES, et al. The efficacy of minocycline against methotrexate-induced pulmonary fibrosis in mice. Eur Rev Med Pharmacol Sci. 2013;17(24):3334-3340.
  • Shiromwar SS, Chidrawar VR. Combined effects of p-coumaric acid and naringenin against doxorubicin-induced cardiotoxicity in rats. Phcog Res. 2011;3:214-219. doi:10.4103/0974-8490.85012
  • Sabitha R, Nishi K, Gunasekaran VP, et al. p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models. Chem Biol Interact. 2020;321:109044. doi:10.1016/j.cbi.2020.109044
  • Ali YA, Ahmed AAE, Abd El-Raouf OM, Elkhoely A, Gad AM. Polydatin combats methotrexate-induced pulmonary fibrosis in rats: Involvement of biochemical and histopathological assessment. J Biochem Mol Toxicol. 2022;36(5):e23019. doi:10.1002/jbt.23019
  • Taha MME, Mohan S, Khediash H, et al. Amelioration of carbon tetrachloride-induced liver injury by p-coumaric acid. Curr Top Nutraceutical Res. 2020;18(4):1-6. doi:10.37290/ctnr2641-452X.18:1-6
There are 38 citations in total.

Details

Primary Language English
Subjects Toxicology, Metabolic Medicine
Journal Section Research Articles
Authors

Selim Demir 0000-0002-1863-6280

Nihal Türkmen Alemdar 0000-0002-8913-8692

Elif Ayazoglu Demir 0000-0001-7188-2176

Ahmet Mentese 0000-0003-2036-5317

Yüksel Aliyazıcıoğlu 0000-0001-9474-4307

Publication Date June 30, 2024
Submission Date May 14, 2024
Acceptance Date June 15, 2024
Published in Issue Year 2024 Volume: 3 Issue: 2

Cite

AMA Demir S, Türkmen Alemdar N, Ayazoglu Demir E, Mentese A, Aliyazıcıoğlu Y. The Therapeutic Effect of p-Coumaric Acid on Lung Toxicity Induced by Methotrexate in Rats. Farabi Med J. June 2024;3(2):57-62. doi:10.59518/farabimedj.1484155

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