Evaluation of the antiulcerogenic activity of violacein and its modulation by the inclusion complexation with beta-cyclodextrin.
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.
Durán
Nelson
N
Biological Chemistry Laboratory, Instituto de Química, Universidade Estadual de Campinas (UNICAMP), C.P. 6184, CEP 13083-970, Campinas, SP, Brazil.
Justo
Giselle Z
GZ
Melo
Patrícia S
PS
De Azevedo
Mariângela B M
MB
Brito
Alba R M Souza
AR
Almeida
Ana B A
AB
Haun
Marcela
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002927:Cimetidine / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D022781:Hepatocytes / Q000187:drug effects; D006851:Hydrochloric Acid / Q000009:adverse effects; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D013312:Stress, Physiological / Q000503:physiopathology; D020122:tert-Butylhydroperoxide / Q000009:adverse effects
D000897:Anti-Ulcer Agents; D003505:Cyclodextrins; D007211:Indoles; D000431:Ethanol; D008315:Malondialdehyde; D002927:Cimetidine; D020122:tert-Butylhydroperoxide; C063155:violacein; D006851:Hydrochloric Acid; D007213:Indomethacin