Alterations of Antitumor and Metabolic Responses in L5178y-R Lymphoma-Bearing Mice After Only 30-Minute Daily Chronic Stress Exposure

Abstract

Aim: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. Materials and Methods: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. Results: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. Conclusion: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research.

Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice

“…However, there is no evidence of catecholamines synthesis by tumors from non-nervous tissues such as lymphomas. In a previous work, we observed that tumor burden was associated with a significant increase in plasmatic norepinephrine in L5178Y-R lymphoma-bearing mice that was independent of adrenergic activation by stress [ 6 ], thus, we hypothesized that L5178Y-R lymphoma cells may be expressing Th and secreting NE, contributing to the observed increase in NE circulating levels. The aims of the present study were to assess the expression of the Th gene in the L5178Y-R lymphoma model, its association with adrenergic innervation, and changes in body composition, tumor volume, and antitumor cytokines response.…”