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Effect of hemin and ascorbic acid on colonic pre-neoplastic lesions induced by azoxymethane in mice KCI 등재
- 언어ENG
- URLhttps://db.koreascholar.com/Article/Detail/341601
pp.156-161
Colorectal cancer (CRC) is the third most prevalent cancer in the world, and heme iron is known to promote the CRC in an animal model. This study was conducted to investigate the effects of ascorbic acid in the presence of hemin on the formation of pre-neoplastic lesions induced by azoxymethane (AOM)/disodium sulfate (DSS) in mice. After acclimation for 1 week, five-week old mice received three s.c. injections (0-2 weeks of the experiment) of AOM [10 mg/kg body weight (BW)] weekly and were treated with 2% DSS in drinking water for the next week to induce aberrant crypt foci (ACF). All animals were fed the AIN-76A purified rodent diet for experimental period of 6 weeks. Experimental groups were then divided into three groups: carboxymethylcellulose (CMC) alone (control), CMC + Hemin, CMC + Hemin + ascorbic acid (AA). The CMC was used as a solvent for hemin. The daily doses were 534 mg/kg BW hemin and 246 mg/kg BW ascorbic acid administered orally. After the colonic mucosa were stained with methylene blue, aberrant crypt foci (ACF), aberrant crypt (AC) and polyps were counted. Lipid peroxidation in liver was evaluated by the thiobarbituric acid-reactive substances (TBARS) assay. The numbers of ACF, AC and large ACF (≥4 AC/ACF) per colon increased in the hemin group compared to the control group, while they decreased significantly in the hemin + ascorbic acid group compared to the control group or hemin group (p<0.01). The number of polyps/colon in the hemin + AA group was significantly decreased compared to the hemin group (p<0.05). In the liver, the TBARS value of the hemin group was significantly higher than that of the control group (p<0.01). Additionally, the TBARS value of the hemin + AA group decreased slightly compared to that of the hemin group. Taken together, these results suggest that hemin can promote colon carcinogenesis in a mouse model and that ascorbic acid has a protective effect against hemin-promoted colon carcinogenesis.
MATERIALS AND METHODS
Experimental materials
Animals and experimental diet
Experimental design
Sample collection
Aberrant crypt foci, aberrant and polyps counts
Thiobarbituric acid reactive substances (TBARS) assay
Statistical analysis
RESULTS
Changes in body weights
Total number of aberrant crypt foci (ACF) and aberrant crypt (AC)
Total number of large aberrant crypt foci (≥4 AC/ACF)
Number of polyps
TBARS values in liver
DISCUSSION
REFERENCES
