The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4 0 -geranyloxy-3 0 -methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with b-cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/ dextran sodium sulfate (DSS) model. Male CD-1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/b-CD or AUR/b-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/b-CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 6 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/b-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/b-CD and AUR/b-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-a, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1b, which were induced in the adenocarcinomas. Our findings indicate that GOFA/b-CD and AUR/b-CD, especially GOFA/b-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.There were $1 million new cases of colorectal cancer (CRC) in 2002 (9.4% of the total cancers). 1 Globally, the mortality of CRC was reported to be 655,000 deaths per year in 2005. 2 There is at least a 25-fold variation in the occurrence of CRC worldwide.1 The highest rates of incidence are in North America, Australia/New Zealand, Western Europe and Japan, especially in Japanese men.1 These large geographic differences for CRC are probably explained by differences in environmental exposures and lifestyles.There are several types of pathogenesis of CRC. 3 Among them, inflammation is linked with CRC development. 4 The risk of CRC in patients with inflammatory bowel disease inflammatory bowel disease; IL: interleukin; iNOS: inducible nitric oxide synthase; NF-jB: nuclear factor-kappaB; Nrf2: NF-E2-related factor 2; TdT: terminal deoxynucleotidyl transferase; Tnf: tumor necrosis factor;

No abstract

No abstract

No abstract

The effects of beta-cyclodextrin (betaCD) inclusion complexation on the ability of violacein to prevent gastric ulceration in mice were studied. Violacein-betaCD inclusion complexes were prepared in 1:1 and 1:2 molar ratios and analysed by differential scanning calorimetry and powder X-ray diffractometry. Violacein previously administered orally at 10 mg/kg significantly reduced indomethacin-induced gastric lesions, as well as 100 mg/kg of cimetidine (positive control). However, betaCD complexation in both molar ratios significantly potentiated the protective action of violacein. In the HCl--ethanol-induced gastric ulcer model, violacein and the 1:2 inclusion complex (10 mg/kg, p.o.) inhibited gastric damage by almost 85%, whereas a 63% reduction was observed for the positive control, lansoprazole, at 30 mg/kg. In contrast, treatment with the 1:1 inclusion complex resulted in almost total disappearance of the antiulcer activity in this model. No significant changes in stress-induced gastric injury were found. In addition, the 1:2 inclusion complex improved the antilipoperoxidant activity of violacein in rat liver cells exposed to t-butyl hydroperoxide, whereas the 1:1 complex was less active than violacein. In summary, the 1:2 betaCD inclusion complex has gastroprotective properties similar to or higher than that of violacein. An increase in mucosal defensive mechanisms and protection against peroxidative damage might be involved.

No abstract

No abstract

No abstract