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|Type:||Artigo de periódico|
|Title:||In Vitro Hepatocyte Cytotoxicity Of A Derivative Antiulcer Compound|
|Abstract:||Dehydrocrotonin (DHC) is a diterpene obtained from Croton cajucara Benth. We have demonstrated that DHC has a potent antiulcerogenic activity on several models of experimentally induced rat gastric ulcers. In order to obtain new derivatives from DHC, with antiulcerogenic properties but lower toxicity, a reduced derivative of the cyclohexenenone moiety of DHC was synthesized. Since the assesment of basal and selective toxicity is the first step in the evaluation of a new drug, we used Hamster chinese fibroblasts (V-79) and primary rat hepatocytes cell cultures for toxicity evaluation of DHC derivative. (For DHC cytotoxicity see poster in the same section). Hepatocytes were isolated from adult male Wistar rats by the method of Guguen-Guillouzo (1986). Four hours after seeding, the unattached cells were discarded and 1 ml/well of fresh medium (without serum) containing various dilutions of DHC derivative was added and incubated for 20 h. Three independent endpoints, MTT (tetrazolium salt) reduction, neutral red uptake (NRU) and nucleic acid content (NAC) were meaured for relative toxicity assesment. A very high toxicity (IC 50 10 uM) was afforded by MTT test, nevertheless for NAC doses up to 120 uM presented results similar to controls. We determine the metabolic capacity of primary culture rat hepatocytes at 4, 24 and 48 h old. A dose related increase in NRU was observed (40%) while the reduction of MTT was lowered, relative to untreated cells. The profile response for MTT and NRU, apparently opposite, suggest a cell defense function (higher number lysosomes) and a P-450 mediated metabolization. A marked age culture dependent cytotoxicity was obtained. Supported: CAPES, PADCT/FINEP and FAPESP obatained.|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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