Dehydrocrotonin and its beta-cyclodextrin complex: cytotoxicity in V79 fibroblasts and rat cultured hepatocytes.
Trans-dehydrocrotonin has antiulcerogenic and antitumor activities. A complex of beta-cyclodextrin with dehydrocrotonin was developed to improve the delivery of dehydrocrotonin. Complex in solid state was evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). X-ray diffraction and scanning electron microscopy studies showed that dehydrocrotonin exists in a semicrystalline state in the complexed form with beta-cyclodextrin. Differential scanning calorimetry studies showed the existence of a complex of dehydrocrotonin with beta-cyclodextrin. The thermal gravimetric analysis studies confirmed the differential scanning calorimetry results of the complex. Free dehydrocrotonin and the dehydrocrotonin/beta-cyclodextrin inclusion complex were assayed in freshly isolated rat hepatocytes and in V79 cells. Cytotoxicity was determined using nucleic acid content, methylthiazoletetrazolium (MTT) reduction and neutral red uptake assays. In all assays, there was a large reduction (3.5-16.1-fold) in the cytotoxicity of dehydrocrotonin in hepatocytes when complexed with beta-cyclodextrin, whereas for V79 cells the decrease in cytotoxicity was 1.7- and 1.87-fold for MTT reduction and nucleic acid content assays, respectively. The lower cytotoxicity of the dehydrocrotonin/beta-cyclodextrin complex compared to free dehydrocrotonin in rat hepatocytes and V79 cells suggests that such a complex may be useful for the administration of dehydrocrotonin in vivo.
Corrêa
Daniel H A
DH
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, SP 13083-970, Brazil. dcorrea@unicamp.br
Melo
Patricia S
PS
de Carvalho
Carlos A A
CA
de Azevedo
Mariângela B M
MB
Durán
Nelson
N
Haun
Marcela
M
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008297:Male; D008855:Microscopy, Electron, Scanning; D009696:Nucleic Acids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013818:Thermogravimetry; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
D045785:Diterpenes, Clerodane; D009696:Nucleic Acids; D047392:beta-Cyclodextrins; C103060:dehydrocrotonin; C031215:betadex