Enhancement of the Antigenotoxic and Antioxidant Actions of Eugenol from Spice Clove and the Stabilizer Gum Arabic on Colorectal Carcinogenesis — Oak Academic Publishing
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Enhancement of the Antigenotoxic and Antioxidant Actions of Eugenol from Spice Clove and the Stabilizer Gum Arabic on Colorectal Carcinogenesis
Postgraduate Program in Medical-Surgical Sciences, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
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School of Medicine, Federal University of Ceará, Fortaleza, Brazil
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School of Medicine, Federal University of Ceará, Fortaleza, Brazil
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School of Medicine, Federal University of Ceará, Fortaleza, Brazil
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Nucleus of Research and Development of Medicines (NPDM), Laboratory of Pharmacology and Preclinical Research, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
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Nucleus for Research and Development of Medicines (NPDM), National Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Brazil
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Nucleus for Research and Development of Medicines (NPDM), National Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Brazil
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Postgraduate Program in Pathology and Medical-Surgical Sciences, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
1 Postgraduate Program in Medical-Surgical Sciences, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
2 School of Medicine, Federal University of Ceará, Fortaleza, Brazil
3 School of Medicine, Federal University of Ceará, Fortaleza, Brazil
4 School of Medicine, Federal University of Ceará, Fortaleza, Brazil
5 Nucleus of Research and Development of Medicines (NPDM), Laboratory of Pharmacology and Preclinical Research, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
6 Nucleus for Research and Development of Medicines (NPDM), National Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Brazil
7 Nucleus for Research and Development of Medicines (NPDM), National Laboratory of Experimental Oncology, Federal University of Ceará, Fortaleza, Brazil
8 Postgraduate Program in Pathology and Medical-Surgical Sciences, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
Spices are defined as any aromatic condiment of plant origin used to alter the flavor and aroma of foods. Besides flavor and aroma, many spices have antioxidant activity, mainly related to the presence in cloves of phenolic compounds, such as flavonoids, terpenoids and eugenol. In turn, the most common uses of gum arabic are in the form of powder for addition to soft drink syrups, cuisine and baked goods, specifically to stabilize the texture of products, increase the viscosity of liquids and promote the leavening of baked products (e.g., cakes). Both eugenol, extracted from cloves, and gum arabic, extracted from the hardened sap of two species of the Acacia tree, are dietary constituents routinely consumed virtually throughout the world. Both of them are also widely used medicinally to inhibit oxidative stress and genotoxicity. The prevention arm of the study included groups: Ia, IIa, IIIa, Iva, V, VI, VII, VIII. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA, EUG, or 10% GA + EUG by gavage. The treatment arm of the study included groups Ib, IIb, IIIb e IVb, IX, X, XI, XII). Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG by gavage. The novelty of this study is the investigation of their use alone and together for the prevention and treatment of experimental colorectal carcinogenesis induced by dimethylhydrazine. Our results show that the combined use of 10% gum arabic and eugenol was effective, with antioxidant action in the colon, as well as reducing oxidative stress in all colon segments and preventing and treating genotoxicity in all colon segments. Furthermore, their joint administration reduced the number of aberrant crypts and the number of aberrant crypt foci (ACF) in the distal segment and entire colon, as well as the number of ACF with at least 5 crypts in the entire colon. Thus, our results also demonstrate the synergistic effects of 10% gum arabic together with eugenol (from cloves), with antioxidant, antigenotoxic and anticarcinogenic actions (prevention and treatment) at the doses and durations studied, in the colon of rats submitted to colorectal carcinogenesis induced by dimethylhydrazine.
Inca-Instituto Nacional de Cancer (Brasil) (2022) Estimate|2023—Cancer Incidence in Brazil/Instituto Nacional de Cancer. INCA, Rio de Janeiro.
Siegel, R.L., Miller, K.D., Fuchs, H.E. and Jemal, A. (2022) Cancer Statistics. CA: A Cancer Journal for Clinicians, 72, 7-33. https://doi.org/10.3322/caac.21708
Morgan, E., Arnold, M., Gini, A., Lorenzoni, V., Cabasag, C.J., Laversanne, M., Vignat, J., Ferlay, J., Murphy, N. and Bray, F. (2023) Global Burden of Colorectal Cancer in 2020 and 2040: Incidence and Mortality Estimates from GLOBOCAN. Gut, 72, 338-344. https://doi.org/10.1136/gutjnl-2022-327736
World Health Organization WHO (2018) Global Cancer Observatory—Globocan.
Pandurangan, A.K., Divya, T., Kumar, K., Dineshbabu, V., Velavan, B. and Sudhandiran, G. (2018) Colorectal Carcinogenesis: Insights into the Cell Death and Signal Transduction Pathways: A Review. World Journal of Gastrointestinal Oncology, 10, 244-259. http://dx.doi.org/10.4251/wjgo.v10.i9.244
Patterson, A.D., Gonzalez, F.J., Perdew, G.H. and Peters, J.M. (2018) Molecular Regulation of Carcinogenesis: Friend and Foe. Toxicological Sciences, 165, 277-283. https://doi.org/10.1093/toxsci/kfy185
Basnet, U., Patil, A.R., Kulkarni, A. and Roy, S. (2021) Role of Stress-Survival Pathways and Transcriptomic Alterations in Progression of Colorectal Cancer: A Health Disparities Perspective. International Journal of Environmental Research and Public Health, 18, Article No. 5525. https://doi.org/10.3390/ijerph18115525
Moradi-Marjaneh, R., Hassanian, S.M., Mehramiz, M., Rezayi, M., Ferns, G.A., Khazaei, M. and Avan, A. (2019) Reactive Oxygen Species in Colorectal Cancer: The Therapeutic Impact and Its Potential Roles in Tumor Progression via Perturbation of Cellular and Physiological Dysregulated Pathways. Journal of Cellular Physiology, 234, 10072-10079. https://doi.org/10.1002/jcp.27881
Silva-Reis, R., Castro-Ribeiro, C., Goncalves, M., Ferreira, T., Pires, M.J., Iglesias-Aguirre, C.E., Cortés-Martín, A., Selma, M.V., Espín, J.C., Nascimento-Goncalves, E., Moreira-Pais, A., Neuparth, M.J., Peixoto, F., Rosa, E., Gama, A., Ferreira, R., Oliveira, P.A. and Faustino-Rocha, A.I. (2022) An Integrative Approach to Characterize the Early Phases of Dimethylhydrazine-Induced Colorectal Carcinogenesis in the Rat. Biomedicines, 10, Article No. 409. https://doi.org/10.3390%2Fbiomedicines10020409
Tsounis, D., Villiotou, V., Melpidou, A., Pantsiou, C., Argyrou, A., Giannopoulou, C., Grigoratou, A., Rontogianni, D., Mantzaris, G.J. and Papatheodoridis, G. (2022) Oxidative Imbalance Increases the Risk for Colonic Polyp and Colorectal Cancer Development. World Journal of Gastrointestinal Oncology, 14, 2208-2223. https://doi.org/10.4251/wjgo.v14.i11.2208
Genotoxicity
Ribeiro, C.C.D., Silva, R.M., Campanholo, V.M.L.P., Ribeiro, D.A., Ribeiro Paiotti, A.P. and Forones, N.M. (2018) Effects of Grape Juice in Superoxide Dismutase and Catalase in Colorectal Cancer Carcinogenesis Induced by Azoxymethane. Asian Pacific Journal of Cancer Prevention, 19, 2839-2844. https://doi.org/10.22034/apjcp.2018.19.10.2839
Dharshini, L.C.P., Rasmi, R.R., Kathirvelan, C., Kumar, K.M., Saradhadevi, K.M. and Sakthivel, K.M. (2022) Regulatory Components of Oxidative Stress and Inflammation and Their Complex Interplay in Carcinogenesis. Applied Biochemistry and Biotechnology, 195, 2893-2916. https://doi.org/10.1007/s12010-022-04266-z
Moaty, M.N., El Ashry, E.S.H., Awad, L.F., Mostafa, A., Abu-serie, M.M. and Teleb, M. (2022) Harnessing ROS-Induced Oxidative Stress for Halting Colorectal Cancer via Thiazolidinedione-Based SOD Inhibitors. ACS Omega, 7, 21267-21279. https://doi.org/10.1021%2Facsomega.2c02410
Srinivas, U.S., Tan, B.W.Q., Vellayappan, B.A. and Jeyasekharan, A.D. (2019) ROS and the DNA Damage Response in Cancer. Redox Biology, 25, Article ID: 101084. https://doi.org/10.1016/j.redox.2018.101084
Ying, J., Yang, L., Yin, J.C., Xia, G., Xing, M., Chen, X., Pang, J., Wu, Y., Bao, H., Wu, X., Shao, Y., Zhu, L. and Cheng, X. (2021) Additive Effects of Variants of Unknown Significance in Replication Repair-Associated DNA Polymerase Genes on Mutational Burden and Prognosis across Diverse Cancers. The Journal for ImmunoTherapy of Cancer, 9, e002336. https://doi.org/10.1136/jitc-2021-002336
Nogacka, A.M., Gómez-Martín, M., Suárez, A., González-Bernardo, O., de Los Reyes-Gavilán, C.G. and González, S. (2019) Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer. International Journal of Molecular Sciences, 20, Article No. 2051. https://doi.org/10.3390/ijms20082051
Koklesova, L., Liskova, A., Samec, M., Qaradakhi, T., Zulli, A., Smejkal, K., Kajo, K., Jakubikova, J., Behzadi, P., Pec, M., Zubor, P., Biringer, K., Kwon, T.K., Büsselberg, D., Sarria, G.R., Giordano, F.A., Golubnitschaja, O. and Kubatka, P. (2020) Genoprotective Activities of Plant Natural Substances in Cancer and Chemopreventive Strategies in the Context of 3P Medicine. EPMA Journal, 11, 261-287. https://doi.org/10.1007/s13167-020-00210-5
FIB-Food Ingredients Brasil No 47—2019. https://revista-fi.com.br/artigos/gomas/gomas-xantana-gelana-carragena-e-outras
Kaddam, L., Fadl-Elmula, I., Eisawi, O.A., Abdelrazig, H.A., Salih, M.A., Lang, F. and Saeed, A.M. (2017) Gum Arabic as Novel Anti-Oxidant Agent in Sickle Cell Anemia, Phase II Trial. BMC Hematology, 17, Article No. 4. https://doi.org/10.1186/s12878-017-0075-y
Braga, V.N.L., Juanes, C.C., Peres Júnior, H.S., Sousa, J.R., Cavalcanti, B.C., Jamacaru, F.V.F. Lemos, T.L.G. and Dornelas, C.A. (2019) Gum Arabic and Red Propolis Protecteting Colorectal Preneoplastic Lesions in a Rat Model of Azoxymethane. Acta Cirúrgica Brasileira, 34, e201900207. https://doi.org/10.1590/s0102-8650201900207
Avelino, A.L.N., Silva, N.V.R.E., Oliveira, G.B., Silva, A.A.S., Cavalcanti, B.C., Jamacaru, F.V.F. and Dornelas, C.A. (2021) Antioxidant and Antigenotoxic Actions of Gum Arabic on the Intestinal Mucosa, Liver and Bone Marrow of Swiss Mice Submitted to Colorectal Carcinogenesis. Nutrition and Cancer, 74, 956-964. https://doi.org/10.1080/01635581.2021.1931699
NCBI National Center for Biotechnology Information (2020) PubChem Compound Summary for CID 3314, Eugenol.
Nejad, S.M., Ozgünes, H. and Basaran, N. (2017) Pharmacological and Toxicological Properties of Eugenol. Turkish Journal of Pharmaceutical Sciences, 14, 201-206. https://doi.org/10.4274/tjps.62207
Khalilzadeh, E., Hazrati, R. and Saiah, G.V. (2016) Effects of Topical and Systemic Administration of Eugenia caryophyllata Buds Essential Oil on Corneal Anesthesia and Analgesia. Research in Pharmaceutical Sciences, 11, 293-302. https://doi.org/10.4103/1735-5362.189297
Taher, Y.A., Samud, A.M., El-Taher, F.E., Ben-Hussin, G., Elmezogi, J.S., Al-Mehdawi, B.F. and Salem, H.A. (2015) Experimental Evaluation of Anti-Inflammatory, Antinociceptive and Antipyretic Activities of Clove Oil in Mice. Libyan Journal of Medicine, 10, Article No. 28685. https://doi.org/10.3402/ljm.v10.28685
Lane, T., Anantpadma, M., Freundlich, J.S., Davey, R.A., Madrid, P.B. and Ekins, S. (2019) The Natural Product Eugenol Is an Inhibitor of the Ebola Virus in Vitro. Pharmaceutical Research, 36, Article No. 104. https://doi.org/10.1007/s11095-019-2629-0
Lou, Z., Letsididi, K.S., Yu, F., Pei, Z., Wang, H. and Letsididi, R. (2019) Inhibitive Effect of Eugenol and Its Nanoemulsion on Quorum Sensing-Mediated Virulence Factors and Biofilm Formation by Pseudomonas aeruginosa. Journal of Food Protection, 82, 379-389. https://doi.org/10.4315/0362-028x.jfp-18-196
Akdemir, F.N.E., Yildirim, S., Kandemir, F.M., Aksu, E.H., Guler, M.C., Kiziltunc Ozmen, H., Kucukler, S. and Eser, G. (2019) The Antiapoptotic and Antioxidant Effects of Eugenol against Cisplatin-Induced Testicular Damage in the Experimental Model. Andrologia, 51, e13353. https://doi.org/10.1111/and.13353
Cui, Z., Liu, Z., Zeng, J., Chen, L., Wu, Q., Mo, J., Zhang, G., Song, L., Xu, W., Zhang, S. and Guo, X. (2019) Eugenol Inhibits Non-Small Cell Lung Cancer by Repressing Expression of NF-κB-Regulated TRIM59. Phytotherapy Research, 33, 1562-1569. https://doi.org/10.1002/ptr.6352
Abdullah, M.L., Hafez, M.M., Al-Hoshani, A. and Al-Shabanah, O. (2018) Anti-Metastatic and Anti-Proliferative Activity of Eugenol against Triple Negative and HER2 Positive Breast Cancer Cells. BMC Complementary and Alternative Medicine, 18, Article No. 321. https://doi.org/10.1186/s12906-018-2392-5
Manikandan, P., Murugan, R.S., Priyadarsini, R.V., Vinothini, G. and Nagini, S. (2010) Eugenol Induces Apoptosis and Inhibits Invasion and Angiogenesis in a Rat Model of Gastric Carcinogenesis Induced by MNNG. Life Sciences, 86, 936-941. https://doi.org/10.1016/j.lfs.2010.04.010
Nasir, O., Wang, K., Foller, M., Bhandaru, M., Sandulache, D., Artunc, F., Ackermann, T.F., Ebrahim, A., Palmada, M., Klingel, K., Saeed, A.M. and Lang, F. (2010) Downregulation of Angiogenin Transcript Levels and Inhibition of Colonic Carcinoma by Gum Arabic (Acacia senegal). Nutrition and Cancer, 62, 802-810. https://doi.org/10.1080/01635581003605920
Larangeira, L.L.S., Taha, M.O., Ferme, A., Lemos, R. and Plaper, H. (1998) Localizacao de lesoes tumorais induzidas pela 1,2-dimetilhidrazina e seu grau de atipia no colon de ratos. Acta Cirúrgica Brasileira, 13. https://doi.org/10.1590/S0102-86501998000300008
Ravnik-Glavac, M., Cerar, A. and Glavac, D. (2000) Animal Model in the Study of Colorectal Carcinogenesis. Pflügers Archiv, 440, R55-R57. https://doi.org/10.1007/s004240000005
Bartosz, G. (2006) Use of Spectroscopic Probes for Detection of Reactive Oxygen Species. Clinica Chimica Acta, 368, 53-76. https://doi.org/10.1016/j.cca.2005.12.039
Akerboom, T.P.M. and Sies, H. (1981) Assay of Glutathione, Glutathione Disulfide, and Glutathione Mixed Disulfides in Biological Samples. Methods in Enzymology, 77, 373-382. https://doi.org/10.1016/S0076-6879(81)77050-2
Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent. Journal of Biological Chemistry, 193, 265-275. https://doi.org/10.1016/S0021-9258(19)52451-6
Smith, C.C., O’Donovan, M.R. and Martin, E. (2006) hOGG1 Recognizes Oxidative Damage Using the Comet Assay with Greater Specificity than FPG or ENDOIII. Mutagenesis, 21, 185-190. https://doi.org/10.1093/mutage/gel019
Nuffer, W., Tall Bull, S., Bakhach, H. and Nuffer, M. (2023) Sweetly Improving Sugars? Reviewing Cinnamon’s Effects on Blood Glucose. Journal of Medicinal Food, 26, 68-73. https://doi.org/10.1089/jmf.2022.0073
Crowe-White, K.M., Jung, S.E., Bragg, A. and Senkus, K.E. (2023) Functional Sugar-Free Chewing Gum Infused with Spices Bolsters Antioxidant Capacity and Phenolic Content of Saliva. Scientific Reports, 13, Article No. 4802. https://doi.org/10.1038/s41598-023-30931-2
Angelopoulou, E., Paudel, Y.N., Papageorgiou, S.G. and Piperi, C. (2022) Elucidating the Beneficial Effects of Ginger (Zingiber officinale Roscoe) in Parkinson’s Disease. ACS Pharmacology & Translational Science, 5, 838-848. https://doi.org/10.1021/acsptsci.2c00104
Nath, M. and Debnath, P. (2022) Therapeutic Role of Traditionally Used Indian Medicinal Plants and Spices in Combating COVID-19 Pandemic Situation. Journal of Biomolecular Structure and Dynamics, 41, 5894-5913. https://doi.org/10.1080/07391102.2022.2093793
Singh, N. and Yadav, S.S. (2022) Ethnomedicinal Uses of Indian Spices Used for Cancer Treatment: A Treatise on Structure-Activity Relationship and Signaling Pathways. Current Research in Food Science, 5, 1845-1872. https://doi.org/10.1016/j.crfs.2022.10.005
Xue, Q., Xiang, Z., Wang, S., Cong, Z., Gao, P. and Liu, X. (2022) Recent Advances in Nutritional Composition, Phytochemistry, Bioactive, and Potential Applications of Syzygium aromaticum L. (Myrtaceae). Frontiers in Nutrition, 9, Article ID: 1002147. https://doi.org/10.3389/fnut.2022.1002147
Haro-González, J.N., Castillo-Herrera, G.A., Martínez-Velázquez, M. and Espinosa-Andrews, H. (2021) Clove Essential Oil (Syzygium aromaticum L. Myrtaceae): Extraction, Chemical Composition, Food Applications, and Essential Bioactivity for Human Health. Molecules, 26, Article No. 6387. https://doi.org/10.3390/molecules26216387
Batiha, G.E., Alkazmi, L.M., Wasef, L.G., Beshbishy, A.M., Nadwa, E.H. and Rashwan, E.K. (2020) Syzygium aromaticum L. (Myrtaceae): Traditional Uses, Bioactive Chemical Constituents, Pharmacological and Toxicological Activities. Biomolecules, 10, Article No. 202. https://doi.org/10.3390/biom10020202
Pandey, V.K., Shams, R., Singh, R., Dar, A.H., Pandiselvam, R., Rusu, A.V. and Trif, M. (2022) A Comprehensive Review on Clove (Caryophyllus aromaticus L.) Essential Oil and Its Significance in the Formulation of Edible Coatings for Potential Food Applications. Frontiers in Nutrition, 9, Article ID: 987674. https://doi.org/10.3389/fnut.2022.987674
Pizzo, J.S., Visentainer, J.V., Da Silva, A.L.B.R. and Rodrigues, C. (2023) Application of Essential Oils as Sanitizer Alternatives on the Postharvest Washing of Fresh Produce. Food Chemistry, 407, Article ID: 135101. https://doi.org/10.1016/j.foodchem.2022.135101
Wlodarska, M., Willing, B.P., Bravo, D.M. and Finlay, B.B. (2015) Phytonutrient Diet Supplementation Promotes Beneficial Clostridia Species and Intestinal Mucus Secretion Resulting in Protection against Enteric Infection. Scientific Reports, 5, Article No. 9253. https://doi.org/10.1038/srep09253
Rodrigues, M., BertoncinI-Silva, C., Joaquim, A.G., Machado, C.D., Ramalho, L.N.Z., Carlos, D., Fassini, P.G. and Suen, V.M.M. (2022) Beneficial Effects of Eugenol Supplementation on Gut Microbiota and Hepatic Steatosis in High-Fat-Fed Mice. Food & Function, 13, 3381-3390. https://doi.org/10.1039/D1FO03619J
Calame, W., Weseler, A.R., Viebke, C., Flynn, C. and Siemensma, A.D. (2008) Gum Arabic Establishes Prebiotic Functionality in Healthy Human Volunteers in a Dose-Dependent Manner. British Journal of Nutrition, 100, 1269-1275. https://doi.org/10.1017/s0007114508981447
Amaral, L.A., da Silva Fleming de Almeida, T., Oliveira de Souza, G.H., Baranoski, A., Souza Maris, R., Bittencourt Junior, F.F., Murino Rafacho, B.P., Duenhas Monreal, A.C., Leite Kassuya, C.A., Milan Brochado Antoniolli-Silva, A.C., Freitas Dos Santos, E. and Oliveira, R.J. (2021) The Use of Natural Fiber-Rich Food Product Is Safe and Reduces Aberrant Crypt Foci in a Pre-Clinical Model. Nutrients, 13, Article No. 2708. https://doi.org/10.3390/nu13082708
Venkatachalam, K., Vinayagam, R., Arokia Vijaya Anand, M., Isa, N.M. and Ponnaiyan, R. (2020) Biochemical and Molecular Aspects of 1,2-Dimethylhydrazine (DMH)-Induced Colon Carcinogenesis: A Review. Toxicological Research (Camb), 9, 2-18. https://doi.org/10.1093/toxres/tfaa004
Lannagan, T.R., Jackstadt, R., Leedham, S.J. and Sansom, O.J. (2021) Advances in Colon Cancer Research: In Vitro and Animal Models. Current Opinion in Genetics & Development, 66, 50-56. https://doi.org/10.1016/j.gde.2020.12.003
Wang, Y., Qi, H., Liu, Y., Duan, C., Liu, X., Xia, T., Chen, D., Piao, H.L. and Liu, H.X. (2021) The Double-Edged Roles of ROS in Cancer Prevention and Therapy. Theranostics, 11, 4839-4857. https://doi.org/10.7150/thno.56747
Wu, K., Zhou, Q. and Ouyang, S. (2021) Direct and Indirect Genotoxicity of Graphene Family Nanomaterials on DNA—A Review. Nanomaterials (Basel), 11, Article No. 2889. https://doi.org/10.3390/nano11112889
Hrycay, E.G. and Bandiera, S.M. (2015) Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer. Advances in Pharmacology, 74, 35-84. https://doi.org/10.1016/bs.apha.2015.03.003
Bucher, J.R. (2019) Chapter 15. Oxidative Stress and Radical-Induced Signalling. In: Baan, R.A., Stewart, B.W. and Straif, K., Eds., Tumour Site Concordance and Mechanisms of Carcinogenesis, International Agency for Research on Cancer, Lyon, 153-157.
Li, W., Li, M. and Qi, J. (2021) Nano-Drug Design Based on the Physiological Properties of Glutathione. Molecules, 26, Article No. 5567. https://doi.org/10.3390/molecules26185567
Hobbs, C.A., Recio, L., Streicker, M., Boyle, M.H., Tanaka, J., Shiga, A. and Witt, K.L. (2015) Comet Assay Evaluation of Six Chemicals of Known Genotoxic Potential in Rats. Genetic Toxicology and Environmental Mutagenesis, 786-788, 172-181. https://doi.org/10.1016%2Fj.mrgentox.2015.03.003
Cordelli, E., Bignami, M. and Pacchierotti, F. (2021) Comet Assay: A Versatile but Complex Tool in Genotoxicity Testing. Toxicological Research (Camb), 10, 68-78. https://doi.org/10.1093/toxres/tfaa093
Muruzabal, D., Collins, A. and Azqueta, A. (2021) The Enzyme-Modified Comet Assay: Past, Present and Future. Food and Chemical Toxicology, 147, Article ID: 111865. https://doi.org/10.1016/j.fct.2020.111865
Hassani, A., Mahmood, S., Enezei, H.H., Hussain, S.A., Hamad, H.A., Aldoghachi, A.F., Hagar, A., Doolaanea, A.A. and Ibrahim, W.N. (2020) Formulation, Characterization and Biological Activity Screening of Sodium Alginate-Gum Arabic Nanoparticles Loaded with Curcumin. Molecules, 25, Article No. 2244. https://doi.org/10.3390/molecules25092244
Abu-Serie, M.M., Hamouda, A.F. and Habashy, N.H. (2021) Acacia senegal Gum Attenuates Systemic Toxicity in CCl4-Intoxicated Rats via Regulation of the ROS/NF-κB Signaling Pathway. Scientific Reports, 11, Article No. 20316. https://doi.org/10.1038/s41598-021-99953-y
Ali, B.H., Al Za’abi, M., Al Suleimani, Y., Manoj, P., Ali, H., Ribeiro, D.A. and Nemmar, A. (2020) Gum Arabic Reduces Inflammation, Oxidative, and Nitrosative Stress in the Gastrointestinal Tract of Mice with Chronic Kidney Disease. Naunyn-Schmiedeberg’s Archives of Pharmacology, 393, 1427-1436. https://doi.org/10.1007/s00210-020-01844-y
Ahmed, N., El-Rayes, S.M., Khalil, W.F., Abdeen, A., Abdelkader, A., Youssef, M., Maher, Z.M., Ibrahim, A.N., Abdelrahman, S.M., Ibrahim, S.F., Abdelrahaman, D., Alsieni, M., Elserafy, O.S., Ghamry, H.I., Emam, H.T. and Shanab, O. (2022) Arabic Gum Could Alleviate the Aflatoxin B1-Provoked Hepatic Injury in Rat: The Involvement of Oxidative Stress, Inflammatory, and Apoptotic Pathways. Toxins (Basel), 14, Article No. 605. https://doi.org/10.3390/toxins14090605
Eslick, S., Thompson, C., Berthon, B. and Wood, L. (2022) Short-Chain Fatty Acids as Anti-Inflammatory Agents in Overweight and Obesity: A Systematic Review and Meta-Analysis. Nutrition Reviews, 80, 838-856. https://doi.org/10.1093/nutrit/nuab059
Aloqbi, A.A. (2020) Gum Arabic as a Natural Product with Antimicrobial and Anticancer Activities. Archives of Pharmacy Practice, 11, 107-112.
Aburel, O.M., Pavel, I.Z., Danila, M.D., Lelcu, T., Roi, A., Lighezan, R., Muntean, D.M. and Rusu, L.C. (2021) Pleiotropic Effects of Eugenol: The Good, the Bad, and the Unknown. Oxidative Medicine and Cellular Longevity, 2021, Article ID: 3165159. https://doi.org/10.1155/2021/3165159
Ghodousi-Dehnavi, E., Hosseini, R.H., Arjmand, M., Nasri, S. and Zamani, Z. (2021) A Metabolomic Investigation of Eugenol on Colorectal Cancer Cell Line HT-29 by Modifying the Expression of APC, p53, and KRAS Genes. Evidence-Based Complementary and Alternative Medicine, 2021, Article ID: 1448206. https://doi.org/10.1155/2021/1448206
Zari, A.T., Zari, T.A. and Hakeem, K.R. (2021) Anticancer Properties of Eugenol: A Review. Molecules, 26, Article No. 7407. https://doi.org/10.3390%2Fmolecules26237407
Hussain, A., Brahmbhatt, K., Priyani, A., Ahmed, M., Rizvi, T.A. and Sharma, C. (2011) Eugenol Enhances the Chemotherapeutic Potential of Gemcitabine and Induces Anticarcinogenic and Anti-Inflammatory Activity in Human Cervical Cancer Cells. Cancer Biotherapy and Radiopharmaceuticals, 26, 519-527. https://doi.org/10.1089/cbr.2010.0925
Bürtin, F., Mullins, C.S. and Linnebacher, M. (2020) Mouse Models of Colorectal Cancer: Past, Present and Future Perspectives. World Journal of Gastroenterology, 26, 1394-1426. https://doi.org/10.3748/wjg.v26.i13.1394
Esmeeta, A., Adhikary, S., Dharshnaa, V., Swarnamughi, P., Ummul Maqsummiya, Z., Banerjee, A., Pathak, S. and Duttaroy, A.K. (2022) Plant-Derived Bioactive Compounds in Colon Cancer Treatment: An Updated Review. Biomedicine & Pharmacotherapy, 153, Article ID: 113384. https://doi.org/10.1016/j.biopha.2022.113384
Barboza, J.N., da Silva Maia Bezerra Filho, C., Silva, R.O., Medeiros, J.V.R. and de Sousa, D.P. (2018) An Overview on the Anti-Inflammatory Potential and Antioxidant Profile of Eugenol. Oxidative Medicine and Cellular Longevity, 2018, Article ID: 3957262. https://doi.org/10.1155/2018/3957262
Caetano, B.F., Baptista Tablas, M., Ribeiro Romualdo, G., Marchesan Rodrigues, M.A. and Barbisan, L.F. (2020) Early Molecular Events Associated with Liver and Colon Sub-Acute Responses to 1,2-Dimethylhydrazine: Potential Implications on Preneoplastic and Neoplastic Lesion Development. Toxicology Letters, 329, 67-79. https://doi.org/10.1016/j.toxlet.2020.04.009
Jiang, Y., Feng, C., Shi, Y., Kou, X. and Le, G. (2022) Eugenol Improves High-Fat Diet/Streptomycin-Induced Type 2 Diabetes Mellitus (T2DM) Mice Muscle Dysfunction by Alleviating Inflammation and Increasing Muscle Glucose Uptake. Frontiers in Nutrition, 8, Article ID: 1039753. https://doi.org/10.3389/fnut.2022.1039753
Liu, W., Chen, G., Dou, K., Yi, B., Wang, D., Zhou, Q. and Sun, Y. (2023) Eugenol Eliminates Carbapenem-Resistant Klebsiella pneumoniae via Reactive Oxygen Species Mechanism. Frontiers in Microbiology, 14, Article ID: 1090787. https://doi.org/10.3389/fmicb.2023.1090787
Helmy, H., Hamid Sadik, N.A., Badawy, L. and Sayed, N.H. (2022) Mechanistic Insights into the Protective Role of Eugenol against Stress-Induced Reproductive Dysfunction in Female Rat Model. Chemico-Biological Interactions, 367, Article ID: 110181. https://doi.org/10.1016/j.cbi.2022.110181
Fathy, M., Abdel-Latif, R., Abdelgwad, Y.M., Othman, O.A., Abdel-Razik, A.H., Dandekar, T. and Othman, E.M. (2022) Nephroprotective Potential of Eugenol in a Rat Experimental Model of Chronic Kidney Injury; Targeting NOX, TGF-β, and Akt Signaling. Life Sciences, 308, Article ID: 120957. https://doi.org/10.1016/j.lfs.2022.120957
Al-Jubori, Y., Ahmed, N.T.B., Albusaidi, R., Madden, J., Das, S. and Sirasanagandla, S.R. (2023) The Efficacy of Gum Arabic in Managing Diseases: A Systematic Review of Evidence-Based Clinical Trials. Biomolecules, 13, Article No. 138. https://doi.org/10.3390/biom13010138
Gouda, E. and Babiker, F. (2022) Gum Arabic Protects the Rat Heart from Ischemia/Reperfusion Injury through Anti-Inflammatory and Antioxidant Pathways. Scientific Reports, 12, Article No. 17235. https://doi.org/10.1038/s41598-022-22097-0