Effect of С60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats.

The application of pristine С60 fullerene aqueous colloid solution (C60FAS; 0.5 mg/kg body weight) for rats experienced acute colitis, either intraperitoneally or intrarectally (1) restores the colonic mucosa healing and epithelial barrier integrity, evidenced by autopsies and histological findings and the normalization of phenolsufonphthalein dye daily excretion; (2) attenuates the consequences of hemorrhages, such as signs of anemia and increased platelet count; (3) improves the liver redox status suppressing the lipid peroxidation (malonic dialdehyde and protein carbonyl group levels tended down) and stimulating the antioxidant defense system (glutathione peroxidase activity grew up). In addition, C60FAS intrarectally increases the monocyte count and decreases content of neutrophil granulocytes, i.e. diminishes the rate of the inflammatory process and activates the processes of colon tissues restoring with monocytes involvement. Therefore, intrarectal administration of C60FAS may serve as an efficient tool of ulcerative colitis therapy.

[Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine].

No liver and colon alterations in rats, caused by cytostatic compounds 5-amino-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one (D1) and 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) when administered over a long time were found, as evidenced by the histopathological data and the data of activity of transaminases, alkaline phosphatase and lactate dehydrogenase in the blood serum. D1 and MI-1 in vivo decrease the total area of DMH-induced colon tumors in rats by 46-60%. Furthermore, D1 and MI-1 partially protect the liver and colon mucosa from toxic effects caused by 1,2-dimethylhydrazine (DMH) reducing DNA oxidative modifications, as evidenced by urine 8-hydroxydeoxyguanosine level. The effects of both compounds are similar, but MI-1 is less toxic for the liver and colon of intact animals possessing more pronounced antitumor activity and protective properties in the setting of chemically induced carcinogenesis.

Impact of dihydropyrrol derivative on the normal colonic mucosa of DMH-induced colon cancer rats compared with 5-fluorouracil.

AIM: To compare the effects of cytostatic compound dihydropyrrol derivative (D1, 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one) and 5-fluorouracil (5-FU) on the normal colonic mucosa of tumor-bearing rats and to estimate the relationships between proliferation of normal colonic mucosa and tumor growth parameters. METHODS: 1,2-dimethylhydrazine (DMH) carcinogenic model was used. Male Wistar rats were treated by dimethylhydrazine (20 mg/kg of body weight (b.w.) weekly) for 20 weeks, by D1 (2.3 mg/kg of b.w. daily) for 7 or 27 weeks, and by 5-FU (45 mg/kg of b.w. weekly) for 7 weeks. The number of tumor and tumor total area in dissected colon, mitotic and crypt fission indices in surrounding colon mucosa were measured and correlations between these parameters were computed. RESULTS: The number of tumor node and tumor total area under the influence of D1 and 5-FU were decreased by 40-54%. D1 administration has resulted in the more gentle effect on surrounding healthy colon mucosa comparing to 5-FU, particularly, on vascular bed and proliferative activity. The changes in colon mucosa proliferative activity correlate with tumor growth parameters depending on the action of D1 or 5-FU. CONCLUSIONS: D1 manifests the same antitumor activity but less toxicity comparing to 5-FU that allow to suggest its possible use as an anticancer mean. Obtained correlations could be useful for better understanding of the processes preceeding the malignant transformation and their pharmaceutical correction.