Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia

Yulia Elkina, Sandra Palus, Anika Tschirner, Kai Hartmann, Stephan Von Haehling, Wolfram Doehner, Ulrike Mayer, Andrew J S Coats, John Beadle, Stefan D. Anker, Jochen Springer

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background Cancer cachexia is thought to be the cause of > 20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia. Methods The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1 mg/kg/d (LD), 10 mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle. Results Ten mg/kg/d tandospirone decreased the loss of body weight (p = 0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p <0.001), while 1 mg/kg/d tandospirone was not effective. Locomotor activity (p = 0.0007) and food intake (p = 0.0001) were increased by HD tandospirone. The weight (p = 0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p <0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13-0.86; p = 0.0495). Conclusion Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome.

Original languageEnglish
Pages (from-to)160-166
Number of pages7
JournalInternational Journal of Cardiology
Volume170
Issue number2
DOIs
Publication statusPublished - Dec 10 2013

Fingerprint

Cachexia
Neoplasms
Placebos
Caspases
Hydrocortisone
Hepatocellular Carcinoma
Norepinephrine
Skeletal Muscle
Eating
Weights and Measures
Survival
tandospirone
Anti-Anxiety Agents
Anorexia
Locomotion
Body Composition
Left Ventricular Function
Stroke Volume
Antidepressive Agents
Atrophy

Keywords

  • Anti-depressant
  • Body composition
  • Cancer cachexia
  • Cardiac function
  • Survival
  • Tandospirone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Elkina, Y., Palus, S., Tschirner, A., Hartmann, K., Von Haehling, S., Doehner, W., ... Springer, J. (2013). Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia. International Journal of Cardiology, 170(2), 160-166. https://doi.org/10.1016/j.ijcard.2013.10.022

Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia. / Elkina, Yulia; Palus, Sandra; Tschirner, Anika; Hartmann, Kai; Von Haehling, Stephan; Doehner, Wolfram; Mayer, Ulrike; Coats, Andrew J S; Beadle, John; Anker, Stefan D.; Springer, Jochen.

In: International Journal of Cardiology, Vol. 170, No. 2, 10.12.2013, p. 160-166.

Research output: Contribution to journalArticle

Elkina, Y, Palus, S, Tschirner, A, Hartmann, K, Von Haehling, S, Doehner, W, Mayer, U, Coats, AJS, Beadle, J, Anker, SD & Springer, J 2013, 'Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia', International Journal of Cardiology, vol. 170, no. 2, pp. 160-166. https://doi.org/10.1016/j.ijcard.2013.10.022
Elkina, Yulia ; Palus, Sandra ; Tschirner, Anika ; Hartmann, Kai ; Von Haehling, Stephan ; Doehner, Wolfram ; Mayer, Ulrike ; Coats, Andrew J S ; Beadle, John ; Anker, Stefan D. ; Springer, Jochen. / Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia. In: International Journal of Cardiology. 2013 ; Vol. 170, No. 2. pp. 160-166.
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abstract = "Background Cancer cachexia is thought to be the cause of > 20{\%} of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia. Methods The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1 mg/kg/d (LD), 10 mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle. Results Ten mg/kg/d tandospirone decreased the loss of body weight (p = 0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p <0.001), while 1 mg/kg/d tandospirone was not effective. Locomotor activity (p = 0.0007) and food intake (p = 0.0001) were increased by HD tandospirone. The weight (p = 0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p <0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49{\%} and 52{\%}, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95{\%} CI: 0.13-0.86; p = 0.0495). Conclusion Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome.",
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AU - Von Haehling, Stephan

AU - Doehner, Wolfram

AU - Mayer, Ulrike

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N2 - Background Cancer cachexia is thought to be the cause of > 20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia. Methods The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1 mg/kg/d (LD), 10 mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle. Results Ten mg/kg/d tandospirone decreased the loss of body weight (p = 0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p <0.001), while 1 mg/kg/d tandospirone was not effective. Locomotor activity (p = 0.0007) and food intake (p = 0.0001) were increased by HD tandospirone. The weight (p = 0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p <0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13-0.86; p = 0.0495). Conclusion Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome.

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