Erythropoietin improves cardiac wasting and outcomes in a rat model of liver cancer cachexia

Background: Erythropoietin administration, which is clinically used in cancer patients with cancer-induced anemia, has also potentially beneficial effects on nonhematopoietic organs. We assessed the effects of erythropoietin on cancer cachexia progression and cardiac wasting compared with placebo using the Yoshida hepatoma model. Methods: Wistar rats were divided in a sham group (n = 10) and a tumor-bearing group (n = 60). The tumor-bearing group was further randomized to placebo (n = 28), 500 Unit/kg/day (n = 16) or 5000 Unit/kg/day of erythropoietin (n = 16). Body composition was measured using nuclear magnetic resonance spectroscopy, cardiac function using echocardiography, physical activity using infrared monitoring system. Results: Tumor-bearing rats with high dose erythropoietin led to a significant improvement on survival compared with placebo (hazard ratio: 0.43, 95% CI: 0.20-0.92, p = 0.030), though low dose erythropoietin did not reach significance (hazard ratio: 0.46, 95% CI: 0.22-1.02, p = 0.056). Loss of body weight, wasting of lean mass, fat mass, and reduced physical activity were ameliorated in rats treated with both low and high doses of erythropoietin (p < 0.05, all). Moreover, reduced left ventricularmass and left ventricular systolic function were also ameliorated in rats treated with low and high doses of erythropoietin (p < 0.05, respectively). Conclusions: Overall, the present data support that cardiac wasting induced by cancer cachexia plays an important rolewhich leads to impaired survival, provided that the erythropoietin could be an effective therapeutic approach for cancer cachexia progression and cardiac wasting. (C) 2016 Elsevier Ireland Ltd. All rights reserved.