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Braz. j. med. biol. res ; 39(6): 801-807, June 2006. ilus, tab
Artigo em Inglês | LILACS | ID: lil-428281


Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg-1 day-1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3 percent for piplartine and 55.1 and 56.8 percent for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

Animais , Feminino , Camundongos , Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Benzodioxóis/uso terapêutico , Piper/química , Piperidinas/uso terapêutico , Piperidonas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , /tratamento farmacológico , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Benzodioxóis/isolamento & purificação , Benzodioxóis/toxicidade , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Transplante de Neoplasias , Piperidinas/isolamento & purificação , Piperidinas/toxicidade , Piperidonas/isolamento & purificação , Piperidonas/toxicidade , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Raízes de Plantas/química , Alcamidas Poli-Insaturadas/isolamento & purificação , Alcamidas Poli-Insaturadas/toxicidade , /patologia , Baço/efeitos dos fármacos , Baço/patologia