Abstract
OBJECTIVES: The aim of this research was to evaluate the chemopreventive activity of Moringa oleifera(MO) leaves in a colitis-associated colon carcinogenesis model. Our hypothesis was that moringa leaves contain bioactive compounds capable of inducing antioxidant systems, reducing the incidence of colonic lesions, as well as modulating the expression of genes involved in the inflammatory response and carcinogenesis. METHODS: Forty male (CD-1) mice were divided into 5 groups (n = 8). G1: Healthy control; G2: Positive control induced with azoxymethane (AOM, 10 mg/Kg body weight, intraperitoneal injection) and three cycles of dextran sulfate sodium (DSS, 1.5% in drinking water); groups G3, G4, G5 were induced with AOM/DSS and supplemented with 5, 10 and 20% of MO, respectively. Morphological and histopathological parameters, induction of glutathione-S-transferase (GST) and quinone reductase (QNO1), lipid peroxidation, myeloperoxidase (MPO) activity, short chain fatty acids (SCFA) production and the expression of genes related to cancer-inflammation were evaluated. RESULTS: Significant differences (p < 0.05) were found for the groups supplemented with 5, 10 and 20% of MO in morphological and histopathological parameters compared to positive control. Regarding the induction of enzymes, GST and QNO1 had an increase up to 2.5 times in the liver and 2.1 times in the colon in groups supplemented with 20% MO (GST > QNO1). A decrease in MPO activity (∼50%), and lipid peroxidation (1.5–2.3 times) were found in groups with 10 and 20% of MO compared to the positive control. All the groups supplemented with MO showed an increase in SCFAs production. G3, G4 exhibited an increase (up to 0.5–0.7 times) in the production of acetic acid, and G5 showed a significant increase (∼3 times) in butyric and propionic acid compared to the positive control (p < 0.05). CONCLUSIONS: The results of this study provide in vivo evidence that MO attenuates the colitis-associated colon cancer in mice through the induction of antioxidant and phase II enzymes as well as the decrease of biomarkers of oxidative stress in the liver and colon. FUNDING SOURCES: This study was supported by Universidad Autónoma de Querétaro (FOFI project) and the University of Illinois at Urbana-Champaign.