Yimer, Getnet(PhD)Gedamu, Shewatatek2018-06-222023-11-062018-06-222023-11-062015-04http://etd.aau.edu.et/handle/123456789/2833Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Epidemiological and experimental studies unveiled the importance of compounds derived from plants in reducing the risk of CRC. Recent metaanalyses demonstrate inverse associations between coffee intake and CRC. The aim of the present study was to evaluate chemopreventive potential of Coffee arabica in DMH-induced colorectal carcinogenesis in the rat model through a two-phase study (initiation and postinitiation). Thirty five female wistar rats were divided into seven equal groups. Rats in group IVII except group VI (received normal saline alone) were given freshly prepared DMH (20 mg/kg body weight, ip) in normal saline and pH adjusted (7.0) in 1mM NaOH, once a week for 5 weeks. Groups II and III were received additional oral dose of Coffee arabica (20 mg/kg and 40 mg/kg body weight, respectively) in the initiation phase. Group IV and V were received the same dose of Coffee arabica given in group II and III, respectively) in the post-initiation phase. Group VII was received low dose aspirin orally. After 10 weeks of treatment period, blood was withdrawn for serum biochemical analysis, then animals were scarified and their colons were subjected to macroscopic and microscopic studies. Taken together, the result of this study showed that well characterized preneoplastic features such as multiple plaque lesions, aberrant crypts and aberrant crypt foci were significantly found in the DMH alone treated group. The numbers were significantly reduced in DMH followed by Coffee arabica or Aspirin treated groups. Histologically different degree of dysplasia and hyperplasia observed in DMH treated group. The simultaneous administration of DMH and Coffee arabica or Aspirin reduced these features. In addition, our results showed that an appreciable counteracts effect of Coffee arabica on serum biomarkers and body weights observed in DMH alone treated rats. The results of this study surmise that the effects of Coffee arabica may be due to the presence of phenolic compounds which have antioxidant activities. It brings suppression of cellular proliferation, inhibits lipid profile elevation and interferes with serum protein and body weight declination. Furthermore, this study was provided that Coffee arabica treatment, in both phases, tended to considerably suppress tumor progression and invasion. The elucidation of the inhibitory effects of Coffee arabica on the progressions and invasion of colorectal preneoplastic lesions is thus of great importance and will provide promising targets for preventive and therapeutic interventions of CRC.enColorectal cancer (CRC)Thesis