الفهرس 
Acknowledgments
Genes affected in colorectal pathogenesisOnly 14 pages are availabe for public view
 |  | from | 183 |  |  |
| | | from | 183 | | |
Abstract
CRC is one of the most dangerous diseases across the world. It is still one of the leading causes of death, and its etiology is known to be a combination of hereditary, environmental, dietary factors and lack of physical activity. Chemoprevention plays a potential role in CRC.
The current study was designed to evaluate the efficacy of Hsd supplementation on colonic aberrant crypt foci, Smad4, Activin A, oxidative stress and antioxidant defense system in DMH induced colon carcinogenesis in male rats. Fifty four male rats were divided into five groups. Control group (8rats) four received 0.5 % carboxy methyl cellulose (CMC) orally once daily and four rats received 0.9 % NaCl subcutaneous injection, twice a week for 2 weeks; Hsd group (8 rats) received Hsd orally at a dose of 25mg/kg body weight per day throughout the experimental period; DMH group (10 rats) were given a subcutaneous injection of DMH at a dose of 20 mg/kg body weight twice a week for 2 weeks; DMH and Hsd (DMH+Hsd) group (10 rats) were injected DMH at a dose of 20 mg/kg body weight twice a week for 2 weeks and received Hsd orally at a dose of 25 mg/kg body weight per day throughout the experimental period and Post initiation (DMH followed by Hsd) group (10 rats) were injected DMH at a dose of 20 mg/kg body weight twice a week for 2 weeks, then after one month received Hsd orally at a dose of 25 mg/kg body weight per day till the end of the experiment.After 13 weeks, the rats were sacrificed. Blood samples were collected in plain tubes for serum separation. Serum was used for the biochemical assay of ALT, AST, ALP, Urea, and Creatinine.
Colon tissue samples were collected homogenized in phosphate buffered saline and stored at -20 oC for biochemical examination of MDA, NO, SOD and GSH by colorimetric method and ELISA assay of activin A. Another Colon tissue samples were collected on RNA later solution and stored at -80 oC for assay of Smad4 and activin A mRNA expression by real time PCR. In addition, colon tissue samples were fixed at 10 % neutral buffered formalin for microscopic count of ACF, immunohistochemistry and histopathological examination. The results of the present study showed a significant increase in aberrant crypt foci count in DMH treated group compared to control group. Hsd treatment either throughout the experimental period or following DMH administration resulted in a significant decrease in ACF count compared to DMH treated rats.
The results of the present study showed a significant decrease in Smad4 mRNA expression and increase in Activin A mRNA expression in DMH treated group compared to control group. Hsd treatment either throughout the experimental period or following DMH administration resulted in a significant increase in Smad4 expression compared to DMH treated rats. Furthermore, Hsd treatment resulted in overexpression of activin A mRNA compared to DMH treated rats.
In addition, the present study showed that DMH treatment results in increase oxidative stress markers (MDA and NO) and decreased antioxidant markers (GSH and SOD) compared to control group. Hsd treatment either throughout the experimental period or following DMH administration resulted in a significant decrease in MDA and NO and increase in GSH and SOD in comparison with DMH treated rats.Histopathological examination of colon of DMH treated rats showed adenomatous polyps with dysplastic changes, hyperplastic changes and hyperchromasia in the lining epithelium of the colon in addition to dense lymphocytic infilteration in the submucosa of the colon when compared to the colon of control group animals, which showed complete healthy colon mucosa, submucosa, musclosa. Hsd treatment to DMH treated rats resulted in adenoma but with mild dysplasia, lymphocytic infiltration and of necrosis in some glandular tissues.