Food Intake In Tumor-bearing Rats Research Articles

Cachexia induced by Yoshida ascites hepatoma in Wistar rats is not associated with inflammatory response in the spleen or brain

Recent data indicate that peripheral, as well as hypothalamic pro-inflammatory cytokines play an important role in the development of cancer cachexia. However, there are only a few studies simultaneously investigating the expression of inflammatory molecules in both the periphery and hypothalamic structures in animal models of cancer cachexia. Therefore, using the Yoshida ascites hepatoma rat's model of cancer cachexia we investigated the gene expression of inflammatory markers in the spleen along with the paraventricular and arcuate nuclei, two hypothalamic structures that are involved in regulating energy balance. In addition, we investigated the effect of intracerebroventricular administration of PS-1145 dihydrochloride (an Ikβ inhibitor) on the expression of selected inflammatory molecules in these hypothalamic nuclei and spleen. We observed significantly reduced food intake in tumor-bearing rats. Moreover, we found significantly decreased expression of IL-6 in the spleen as well as decreased NF-κB in the paraventricular nucleus of rats with Yoshida ascites hepatoma. Similarly, expression of TNF-α, IL-1β, NF-κB, and COX-2 in the arcuate nucleus was significantly reduced in tumor-bearing rats. Administration of PS-1145 dihydrochloride reduced only the gene expression of COX-2 in the hypothalamus. Based on our findings, we suggest that the growing Yoshida ascites hepatoma decreased food intake by mechanical compression of the gut and therefore this model is not suitable for investigation of the inflammation-related mechanisms of cancer cachexia development.

Anti-TNF-alpha antibodies normalized body temperature and enhanced food intake in tumor-bearing rats.

Anorectic weight-losing Fischer 344 rats bearing a methylcholanthrene-induced sarcoma received intraperitoneal injections of rabbit antiserum raised against murine tumor necrosis factor (TNF)-alpha at 14, 18, and 24 days after tumor induction. Treatment of tumor-bearing rats with TNF antiserum partially reversed the tumor-induced reduction in food intake compared with tumor-bearing rats that received control serum. In the same tumor-bearing animals, treatment with TNF antiserum delayed the onset and significantly reduced the decline in mean 12-h daytime and nighttime intra-abdominal temperatures on days 18-25. However, anti-TNF antibody treatment did not alter the declines in carcass weight or motor activity measured from day of tumor induction until death or reduce the tumor burden at death. We conclude that an endogenous TNF response may be one of the factors involved in the development of cancer anorexia and that this cytokine has temperature-lowering properties.