Abstract

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

Highlights

  • Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries (Mathers et al, 2008)

  • DMH is metabolized in liver to azoxymethane and methylazoxymethanol which is further transported to colon and elicits oxidative stress by methylating biomolecules of colonic epithelial cells leading to inflammation and tumor promotion (Hamiza et al, 2012)

  • Biochemical analysis of colon tissue cleared that DMH caused a significant increase in the levels of LPO, NO, and GSH and in the activities of Super oxide dismutase (SOD) and glucose-6-phosphte dehydrogenase (G6PD), Catalase activity (CAT) activity was significantly decreased

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Summary

Introduction

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries (Mathers et al, 2008). Several studies focused on the importance of pro- and anti-oxidant indicators, as markers of chemoprevention for many cancers, by natural and synthetic compounds (Balasenthil et al, 2000; Devasena et al, 2006; Ghadi et al, 2009). One of these antioxidants is Quercetin (Q), which increased the sensitivity of resistant colorectal tumors with microsatellite instability to the chemotherapy drug, 5-fluorouracil (Xavier et al, 2011), suppressed azoxymethane-induced hyperproliferation and focal hyperplasia in the colon (Deschner et al, 1991), and reduced intestinal tumor formation (Akagi et al, 1995). Sodium gluconate (GNA) promoted growth performances of nursery pigs by increasing intestinal beneficial bacteria population and

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