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Basic Clin Pharmacol Toxicol ; 119(1): 41-50, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26709053

RESUMO

This study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd-1) against Walker-256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd-1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro-apoptotic protein expression (Bax and p53), while the expression of the anti-apoptotic protein Bcl-2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd-1 treatment. However, significant splenomegaly was evident in animals that received Syd-1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd-1 against Walker-256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.


Assuntos
Antineoplásicos/farmacologia , Carcinoma 256 de Walker/tratamento farmacológico , Sidnonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Catalase/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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