Metformin reduces the stimulatory effect of obesity on in vivo Walker-256 tumor development and increases the area of tumor necrosis.

AIMS: The objective of this study was to analyze the influence of obesity and insulin resistance on tumor development and, in turn, the effect of insulin sensitizing agents. MAIN METHODS: Male offspring of Wistar rats received monosodium glutamate (400mg/kg) (obese) or saline (control) from the second to sixth day after birth. Sixteen-week-old control and obese rats received 5×10(5) Walker-256 tumor cells, subcutaneously injected into the right flank. Some of the obese and control rats received concomitant treatment with metformin (300mg/kg) by gavage. At the 18th week, obesity was characterized. The percentage of rats that developed tumors, the tumor relative weight and the percentage of cachexia incidence were analyzed. The tumor tissue was evaluated histologically by means of hematoxylin and eosin staining. KEY FINDINGS: Metformin did not correct the insulin resistance in obese rats. The tumor development was significantly higher in the obese group, whereas metformin treatment reduced it. After pathological analysis, we observed that the tumor tissues were similar in all groups except for adipocytes, which were found in greater quantity in the obese and metformin-treated obese groups. The area of tumor necrosis was higher in the group treated with metformin when compared with the untreated one. SIGNIFICANCE: Metformin reduced Walker-256 tumor development but not cachexia in obese rats. The reduction occurred independently of the correction of insulin resistance. Metformin increased the area of necrosis in tumor tissues, which may have contributed to the reduced tumor development.

Comparison of the anti-neoplastic effects of dirhodium(II) tetrapropionate and its adducts with nicotinate and isonicotinate anions in mice bearing Ehrlich tumors.

Rhodium(II) propionate, [Rh2(prop)4], and its adduct with nicotinate (nic-) and isonicotinate (isonic-) anions, [Rh2(prop)4(nic)2](2-) and [Rh2(prop)4(isonic)2](2-), respectively, were prepared for study. The compound effects on the survival rate of mice bearing Ehrlich ascites tumors were tested and presented in the form of a survival table, and analyzed by the Mantel-Haenszel chi-square test for N animals in each group. The survival rates of animals were significantly higher than that of control group (P<0.001) without distinguishing among the experimental groups. The estimated probability for an animal in the control group to survive up to the end of the observation period (30 days) was below 33%, whereas the animal groups in the treated group with complex, and its nicotinate and isonicotinate groups showed 85%, 85% and 90%, respectively, of surviving over the same period. The T/C values (survival average of the animals treated group/survival average of the animals control group) were obtained for each compounds being for the dirhodium propionate T/C=250, and for its adducts with nicotinate and isonicotinate anions, 267 and 264, respectively.

Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis.

Arachidonic acid (AA)-induced cytotoxicity was evaluated in leukocytes: the human leukemia cell lines HL-60, Jurkat and Raji and in rat lymphocytes. Such cytotoxicity was dose- and time-dependent. At concentrations below 5 microM, AA was not toxic; at 10-400 microM, AA induced apoptosis and at concentrations beyond 400 microM, necrosis. The minimum exposure time to trigger cell death was of around 1 h, but the effect was increased by longer exposure times until 6-24 h. Apoptosis was morphologically characterized by a decrease in cell and nuclear volume, chromatin condensation and DNA fragmentation and the presence of lipid bodies, without changes in organelle integrity. Biochemically, AA-induced apoptosis was associated with internucleosomal fragmentation and caspase activation, evaluated by PARP cleavage and the use of a caspase inhibitor. Necrosis was characterized by increased cell volume, presence of loose chromatin, appearance of vacuoles, loss of membrane integrity and of the definition of organelles. The apoptotic effect of AA was studied as to oxidative-reductive imbalance and the participation of eicosanoids. Apoptotic AA treatment was accompanied by an increase in the quantity of thiobarbituric acid reactive substances (TBARS), low-level chemiluminescence and in the glutathione disulfide/reduced glutathione ratio, indicating oxidative stress. The addition of tocopherol, ascorbate, prostaglandin E2 and lipoxygenase inhibitors delayed cell death, whereas the inhibition of cyclooxygenase promoted AA-induced cell death. Cell treatment with AA was accompanied by increased cellular production of LTB4. AA, therefore, is cytotoxic at physiological and supraphysiological concentrations, causing apoptosis and necrosis. Cell treatment with apoptotic concentrations of AA involves oxidative stress and changes in eicosanoid biosynthesis.

Apoptosis induced by metal complexes and interaction with dexamethasone.

Apoptosis induced by rhodium II amidate, rhodium II propionate, cisplatin and interactions with dexamethaxone were studied on some human leukemia cell lines Raji, Jurkat and U937. Apoptosis was studied by flow cytometry, agarose gel electrophoresis and morphological analysis. Rhodium II propionate induced apoptosis in all the three cell lines, Rhodium II amidate, in the lymphoid cell lines Jurkat and Raji, and cisplatin, only in the Jurkat, a T lymphoid cell line. It has also been observed that the addition of dexamethasone enhances the apoptosis index only in U937, a monocytic line with a glucocorticoid receptor bearing.

Acao da 3,5,3'-triiodotironina ('T IND.3') sobre a evolucao do carcinossarcoma 256 de Walker / Action of 3,5,3'- triiodothyronine('T IND.3') on Walkers 256 carcinosarcoma development

Com o objetivo de verificar os efeitos da inoculacao de triiodotironina('T IND. 3') em animais portadores de tumor de Walker, os autores propuseram este estudo experimental utilizando ratos Wistar portadores da forma ascitica e da forma solida do referido tumor e camundongos Balb/c isogenicos para estudo da ativacao macrofagica. Os animais foram tratados com 'T IND. 3'20 *g/100g de peso e os resultados obtidos submetidos aos testes estatisticos do Chi-quadrado de Mann-Whitney. Os autores concluem que este hormonio aumenta a sobrevida de ratos portadores do tumor de Walker, porem, sem interferir no peso da massa tumoral. Quanto ao espraiamento de macrofagos, o 'T IND. 3' promoveu aumento significativo quando injetado na cavidade peritonal de camundongos. Tais resultados talvez possam ser explicados pela propria ativacao macrofagica e pela sintese do Fator de Necrose Tumoral(FNT), entre outros fatores.

Alteraçäo da resposta inflamatória e imunológica em animais portadores de tumor experimental / Alteration on inflammatory and immunological response in animal carriers of experimental tumor

Os autores estudaram em camundongos portadores de tumor de Walker as alteraçöes de resposta a agente inflamatório e as modificaçöes de reaçöes imunológicas, assim como o período no qual se tornam evidentes. Usaram como agente inflamatório a carragenina e como parâmetro imunológico o teste de hipersensibilidade ao BCG. As conclusöes foram que os animais portadores de tumor apresentam diminuiçäo na capacidade de resposta inflamatória inespecífica à carragenina e ao CBG, assim como no teste de hipersensibilidade tardia ao BCG

Açäo da cimetidina na sobrevida de camundongos inoculados com tumor de Ehrlich / Action of cimetidine on the survival of mice inoculated with Ehrlich's tumor

Os autores estudaram o efeito da cimetidina na sobrevida de camundongos inoculados com o tumor de Ehrlich e concluíram que a droga aumenta a sobrevida desses animais, sugerindo ainda uma açäo imunomoduladora dessa substância

Efeitos anti-tumorais de drogas anti-H2 / Antitumor effects of histamine H2 receptor blockaders

Os autores estudaram a sobrevida de camundongos inoculados com o tumor de Ehrlich e concluíram que a famotidina e a ranitidina aumentaram a sobrevida destes aimais. Os autores também descreveram que a cimetidina, famotidina e a ranitidina näo alteram a hipersensibilidade tardia do BCG

Estrógeno em tumor de Ehrlich: estudo da sobrevida e avaliaçäo da resposta imunológica / Estrogen in Ehrlich's tumor survival study and immune response evaluation

Estudou-se a sobrevida de camundongos inoculados com tumor de Ehrlich na vigência de tratamento estrogênico, e concomitantemente fêz-se uma avaliaçäo da atividade imunológica em um grupo paralelo. Concluiu-se que os estrógenos aceleram a mortalidade de camundongos machos portadores de tumor de Ehrlich e näo provocavam alteraçöes no número de macrófagos e atividade fagocitária em resposta à inflamaçäo. Os camundongos que receberam tumor de Ehrlich também näo apresentaram diferenças em relaçäo ao grupo de camundongos normais