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.

Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica / Study of morphological alterations of the adrenal glands in the neoplastic cachexia

O câncer em estágio avançado cursa com alterações nutricionais e metabólicas que caracterizam o estado de caquexia neoplásica. Em situações de comprometimento da homeostasia, a glândula adrenal tem papel fundamental na resposta neuroendócrina. Para estudar as alterações morfológicas da adrenal no desenvolvimento do câncer associado à caquexia, utilizamos o modelo experimental de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais foram sacrificados 12 dias após inoculação tumoral e as adrenais removidas para análise histopatológica por meio da coloração porhematoxilina-eosina. Foram avaliados os parâmetros nutricionais, índice de caquexia e peso das adrenais. Os animais com tumor apresentaram índice de caquexia de 16,6 ± 4%. A média do peso das adrenais foi significativamente maior no grupo tumor (40 mg ± 10) do que no controle (25 mg ± 3). O córtex adrenal dos animais com caquexia apresentou hipertrofia das camadas fasciculada e reticular, exibindo espongiócitos volumosos; a região medular apresentou congestão e estase vascular. Os resultados foram semelhantes nos animais do grupo pair fed e do grupo alimentado ad libitum. Animais com caquexia devido ao câncer apresentam comprometimento morfológico da glândula adrenal que exibe alterações relacionadas à resposta de estresse, compatíveis com maior secreção de catecolaminas e ativação do eixo hipotálamo-hipófise-adrenal.

Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia.When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional parameters, cachexia index and adrenal glands weight, were evaluated. Animals with tumor presented cachexia index of 16,6 ± 4%. Adrenal glands average weight was significantly higher in the tumor group (40 mg ± 10) than in the control group (25 mg ± 3). Adrenal cortex of animals with cachexia showed hypertrophy of the zona fasciculata and reticular layer, with voluminous spongiocytes; vascular congestion and stasis were observed in the medullar region. Results were similar in the pairand ad libitum-fed groups. Animals with cancer cachexia showed compromised morphology of the adrenal glands which showed alterations related to stress response, suggesting increased cathecolamine secretion and activation of the hypothalamus-pituitary-adrenal axis.