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EFFICACY OF INTRA-PERITONEAL ADMINISTRATION OF METFORMIN AND 5-FLUORURACIL IN PREVENTION OF INDUCED-COLORECTAL ABERRANT CRYPT FOCI IN MICE
علاء غني حسين مبارك
Authors : ABDULKAREEM H.ABD, ALAA GHANI HUSSEIN, AHMED SALIM MAHMOOD
Objective: The aim of this study is to investigate the anti-proliferative effect of metformin in comparison with 5-fluoruracil (5-FU) in induced-colorectal ACF in mice, and to evaluate the activity of metformin as chemo preventive drug in colorectal cancer when given oral and intra-peritoneal route. Methods: Sixty albino BALB/c mice were allocated into five groups, the groups given azoxymethane (AOM) as inducer for ACF once weekly for two weeks. Group A treated with normal saline injection and considered as positive control; Group B treated with metformin orally for four weeks, Group C treated with intra-peritoneal (i.p.) metfromin and group D treated with i.p injection of 5-FU. Group E did not receive treatment and consider as negative control. The started one week after the second dose of AOM. The body weight has been measured weekly, while fasting blood sugar (FBS) has been measured at the end of the experiment. Then, all animals were sacrificed and their colon and rectum have been removed for counting the number of ACF and the anti-proliferative effect of metformin and 5-FU on colonic epithelium using proliferating cell nuclear antigen (PCNA) labeling index (LI). Results: Metformin has the ability to prevent the ACF without causing any change in the level of FBS. Both metformin and 5-FU have significant anti-proliferative activity against proliferation of colonic epithelium. Intraperitoneal administration of metformin has significant chemo preventive effect and anti-proliferative effect than oral administration so as its efficacy become close to that of 5-FU without significant difference between them. Conclusion: Intra-peritoneal administration of metformin can prevent ACF significantly than oral administration with no change in FBS during the course of the treatment compared to 5-FU. Keywords: Metformin; 5- fluorouracil; Aberrant crypt foci; Chemoprevention.

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February 29, 2014