Abstract
BackgroundAzoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer and oxidative stress in rats. Clinical studies continue to support the notion that oxidative stress is mediated by hyperhomocysteinemia, elevated serum homocysteine level.ObjectiveThis study aimed to investigate the preventive effect of folate and vitamin B12 against AOM‐induced hyperhomocysteinemia, oxidative stress and carcinogenesis in rat colon.MethodsSprague‐Dawley rats were randomly divided into 20 groups (7 rats/group). Control group was fed a basal diet; AOM‐treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas 12 groups were received daily doses of oral supplementation of folate or vitamin B12 in the presence or absence of AOM injection. Another 6 groups of rats were examined for the potential synegestic effect of both folate and vitamin B12 supplementation. All animals were continuously fed ad‐libitum until 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, and homogenized for biochemical measurements of homocysteine, folate, vitamins B12, oxidative stress indices.ResultsOur results showed that AOM‐induced ACF development and pathological changes in the colonic mucosal tissues. Hyperhomocysteinemia and oxidative stress were associated with AOM‐mediated colon carcinogenesis. In rat colonic cells, the concomitant treatment of AOM with folate or vitamin B12 significantly ameliorated the cytotoxic effects of AOM in a dose‐dependent manner.ConclusionThe results of this study provide in‐vivo evidence that folate and vitamin B12 reduced the AOM‐induced colon cancer in rats, through combating hyperhomocysteinemia and oxidative stressSupport or Funding InformationThis research was supported by Internal Grant Funding (IG/AGR/FOOD/14/2), College of Agricultural and Marine Sciences, Sultan Qaboos University
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