Open AccessUrsodeoxycholic acid treatment in a rat model of cancer cachexia
Author(s) -
Tschirner Anika,
von Haehling Stephan,
Palus Sandra,
Doehner Wolfram,
Anker Stefan D.,
Springer Jochen
Publication year - 2012
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1007/s13539-011-0044-4
Subject(s) - cachexia , ursodeoxycholic acid , adipose tissue , endocrinology , medicine , weight loss , proinflammatory cytokine , white adipose tissue , skeletal muscle , wasting , placebo , cancer , inflammation , obesity , pathology , alternative medicine
Background Cancer cachexia is characterized by loss of both adipose and skeletal muscle tissue and by an increased production of proinflammatory cytokines. Ursodeoxycholic acid (UDCA), a bile acid used for centuries in the treatment of liver disease, is known to confer anti‐inflammatory and anti‐apoptotic effects as well as beneficial effects on mitochondrial integrity and cell signaling. We hypothesized that UDCA ameliorates the wasting process in the Yoshida hepatoma tumor model. In addition, we sought to establish if UDCA exerts beneficial effects on survival in this model. Methods and results Forty‐seven male rats were inoculated intraperitoneally with 10 8 Yoshida hepatoma AH‐130 cells and treated with placebo or one of two different doses of UDCA, 25 or 100 mg/kg daily. Body weight, body composition, and activity indicators were measured over the course of study up to day 16. UDCA treatment had no effect on tumor growth, loss of body weight, and loss of fat mass. Compared with placebo, low‐dose UDCA improved tissue loss in the lung ( p = 0.022) and tended to reduce tissue loss in brown adipocytes ( p = 0.06), gastrocnemius muscle ( p = 0.06), extensor digitorum longus muscle ( p = 0.09), and soleus muscle ( p = 0.07). Compared with placebo, high‐dose UDCA tended to reduce the loss of lean body mass ( p = 0.06), lung tissue ( p = 0.1), white adipose tissue ( p = 0.11), and gastrocnemius muscle ( p = 0.11). The activity and food intake were not altered in tumor‐bearing rats by either dose of UDCA. Both doses tended to decrease the mortality rate in tumor‐bearing rats, (hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.17–1.04; p = 0.061 for low‐dose UDCA; HR, 0.44; 95% CI, 0.18–1.05; p = 0.065 for high‐dose UDCA). Conclusion UDCA treatment in the Yoshida hepatoma model showed a trend towards attenuation of tissue loss in animals with progressive weight loss in cancer cachexia. Tumor growth and activity indicators were not altered. Both doses of UDCA tended to reduce the mortality rates in tumor‐bearing animals. Larger studies with longer follow‐up are required to verify these findings.