~ 22 ~ International Journal of Herbal Medicine 2023; 11(1): 22-29 E-ISSN: 2321-2187 P-ISSN: 2394-0514 www.florajournal.com IJHM 2023; 11(1): 22-29 Received: 12-10-2022 Accepted: 16-11-2022 Nayanna De Oliveira Ramos Melo Postgraduate Program in Medical-Surgical Sciences, School of Medicine, Federal University of Ceará (UFC), Fortaleza - CE, Brazil Matheus De Sousa Silva School of Medicine, Federal University of Ceará (UFC), Fortaleza-CE, Brazil Weslei Pires Lima School of Medicine, Federal University of Ceará (UFC), Fortaleza-CE, Brazil Francisco Vagnaldo Fechine Jamacaru Nucleus of Research and Development of Medicines (NPDM), Laboratory of Pharmacology and Preclinical Research, School of Medicine, Federal University of Ceará (UFC), Fortaleza-CE, Brazil Bruno Coêlho Cavalcanti Nucleus for Research and Development of Medicines (NPDM), National Laboratory of Experimental Oncology, Federal University of Ceará (UFC), Fortaleza-CE, Brazil Antônio Adailson De Sousa Silva Nucleus for Research and Development of Medicines (NPDM), National Laboratory of Experimental Oncology, Federal University of Ceará (UFC), Fortaleza-CE, Brazil Conceição Aparecida Dornelas Postgraduate Program, Department of Pathology and Medical-Surgical Sciences, School of Medicine Federal University of Ceará (UFC), Fortaleza - CE, Brazil Corresponding Author: Nayanna De Oliveira Ramos Melo Postgraduate Program in Medical-Surgical Sciences, School of Medicine, Federal University of Ceará (UFC), Fortaleza - CE, Brazil Effect of eugenol and gum arabic on oxidative stress and genotoxicity in rat spleen, kidney and lung tissue following colorectal carcinogenesis Nayanna De Oliveira Ramos Melo, Matheus De Sousa Silva, Weslei Pires Lima, Francisco Vagnaldo Fechine Jamacaru, Bruno Coêlho Cavalcanti, Antônio Adailson De Sousa Silva and Conceição Aparecida Dornelas DOI: https://doi.org/10.22271/flora.2023.v11.i1a.849 Abstract Genetic mutations are linked to cancer. We evaluated gum arabic (GA) and eugenol (EUG) on systemic genotoxicity (spleen, kidney, lung) in rats with DMH-induced colorectal carcinogenesis. The prevention arm, once a week for 20 weeks, the controls received saline while the experimental groups received DMH at 20 mg/kg. During the same period and for an additional 9 weeks, the animals received water, GA, EUG or GA + EUG. The treatment arm, once a week for 20 weeks, the controls received saline while the experimental groups received DMH at 20 mg/kg. During the subsequent 9 weeks, the animals received water, GA, EUG or GA + EUG. The spleen, kidneys and lungs were harvested for genotoxicity evaluation. Genotoxicity was significantly less severe in spleen and kidney tissue in Group VIII and in Group XII, reflecting the synergistic antioxidant and antigenotoxic effect of GA and EUG administered in rats with DMH-induced colorectal carcinogenesis. Keywords: Eugenol, gum arabic, carcinogenesis, antimutagenic agents 1. Introduction Colorectal carcinogenesis involves the progressive accumulation of multiple genetic mutations. Mutations involving the genes p53 and Kras [1] cause loss of function in tumor suppressor genes and gain of function in oncogenes (antagonists) [2] , which in turn contribute directly to the development of colorectal cancer [3] . DMH (1, 2-dimethylhydrazine) is widely used in animal colorectal carcinogenesis models. Metabolically activated in the liver via cytochrome P450, DMH initially oxidizes into azomethane, which is converted into azoxymethane (AOM). AOM is then hydroxylated into methylazoxymethanol (MAM) and excreted to the colon via the bile. MAM is in turn converted by bacterial β-glucuronidase into the methyldiazonium ion-a powerful DNA alkylating agent. The process induces oxidative stress, resulting in genetic damage and mutations in colon cells [4] . Since the active carcinogen is transported by the blood stream, other organs in the body may be directly affected [5] . The mutagenic activity of DMH and AOM is initiated by the methylation of guanine at the N- 7 position. By donating a proton, the alkylated guanine is paired with thymidine rather than with cytosine, inducing changes in the bases. This is followed by further replication, with mispairing of guanine to thymine and cytosine to adenine, favoring the emergence of mutations [5] . The oxidative stress resulting from exposure to DMH has been shown to damage the DNA in rodent colon cells and in several other tissues, such as the liver, kidneys and heart [4] and the stomach and lungs [6] . DMH-induced colon carcinogenesis triggers an insufficient immune response [7] , followed by inhibition of the antioxidant system from oxidative stress, increased oxidative damage to proteins and lipids in the spleen [8] , lung metastasis [9] , and the formation of a large number of alkylated DNA adducts in the kidneys [10] . Much research has been conducted to explore the genotoxic mechanisms involved in colorectal carcinogenesis [11] , in some cases in order to identify natural compounds, such as gum arabic (GA) and eugenol (EUG), capable of preventing or treating carcinogenesis and its systemic repercussions. Natural compounds often have fewer side effects and lower toxicity than allopathic treatments, without detriment to their biological properties, making them an important field of study [12-13] .