The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy

Jochen Springer, Anika Tschirner, Kai Hartman, Stephan Von Haehling, Stefan D. Anker, Wolfram Doehner

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background Cachexia is a common complication of cancer and may be responsible for 22% of all cancer-related deaths. The exact cause of death in cancer cachexia patients is unknown. Recently, atrophy of the heart has been described in cancer cachexia animal models, which resulted in impaired cardiac function and is likely to contribute to mortality. In cancer patients hyperuricaemia independent of tumour lysis syndrome is often associated with a worse prognosis. Xanthine oxidase (XO) metabolizes purines to uric acid and its inhibition has been shown to improve clinical outcome in patients with chronic heart failure. Methods The rat Yoshida AH-130 hepatoma cancer cachexia model was used in this study. Rats were treated with 4 or 40 mg/kg/d oxypurinol or placebo starting one day after tumour-inoculation for maximal 15 days. Cardiac function was analyzed by echocardiography on day 11. Results Here we show that inhibition of XO by oxypurinol significantly reduces wasting of the heart and preserves cardiac function. LVEF was higher in tumour-bearing rats treated with 4 mg/kg/d (61 ± 4%) or 40 mg/kg/d (64 ± 5%) oxypurinol vs placebo (51 ± 3%, both p <0.05). Fractional shortening was improved by 4 mg/kg/d (43 ± 3%) oxypurinol vs placebo (30 ± 2, p <0.05), while 40 mg/kg/d oxypurinol (41 ± 5%) did not reach statistical significance. Cardiac output was increased in the 4 mg/kg/d dose only (71 ± 11 mL/min vs placebo 38 ± 4 mL/min, p <0.01). Conclusion Inhibition of XO with oxypurinol has beneficial effects on cardiac mass and function in a rat model of severe cancer cachexia, suggesting that XO might be a viable drug target in cancer cachexia.

Original languageEnglish
Pages (from-to)3527-3531
Number of pages5
JournalInternational Journal of Cardiology
Volume168
Issue number4
DOIs
Publication statusPublished - Oct 9 2013

Fingerprint

Oxypurinol
Cachexia
Xanthine Oxidase
Cardiomyopathies
Neoplasms
Placebos
Tumor Lysis Syndrome
Uric Acid
Cardiac Output
Atrophy
Echocardiography
Cause of Death
Hepatocellular Carcinoma

Keywords

  • Cancer cachexia
  • Cardiac function
  • Heart
  • Oxypurinol
  • Uric acid
  • Xanthine oxidase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Springer, J., Tschirner, A., Hartman, K., Von Haehling, S., Anker, S. D., & Doehner, W. (2013). The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy. International Journal of Cardiology, 168(4), 3527-3531. https://doi.org/10.1016/j.ijcard.2013.05.063

The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy. / Springer, Jochen; Tschirner, Anika; Hartman, Kai; Von Haehling, Stephan; Anker, Stefan D.; Doehner, Wolfram.

In: International Journal of Cardiology, Vol. 168, No. 4, 09.10.2013, p. 3527-3531.

Research output: Contribution to journalArticle

Springer, J, Tschirner, A, Hartman, K, Von Haehling, S, Anker, SD & Doehner, W 2013, 'The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy', International Journal of Cardiology, vol. 168, no. 4, pp. 3527-3531. https://doi.org/10.1016/j.ijcard.2013.05.063
Springer, Jochen ; Tschirner, Anika ; Hartman, Kai ; Von Haehling, Stephan ; Anker, Stefan D. ; Doehner, Wolfram. / The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy. In: International Journal of Cardiology. 2013 ; Vol. 168, No. 4. pp. 3527-3531.
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abstract = "Background Cachexia is a common complication of cancer and may be responsible for 22{\%} of all cancer-related deaths. The exact cause of death in cancer cachexia patients is unknown. Recently, atrophy of the heart has been described in cancer cachexia animal models, which resulted in impaired cardiac function and is likely to contribute to mortality. In cancer patients hyperuricaemia independent of tumour lysis syndrome is often associated with a worse prognosis. Xanthine oxidase (XO) metabolizes purines to uric acid and its inhibition has been shown to improve clinical outcome in patients with chronic heart failure. Methods The rat Yoshida AH-130 hepatoma cancer cachexia model was used in this study. Rats were treated with 4 or 40 mg/kg/d oxypurinol or placebo starting one day after tumour-inoculation for maximal 15 days. Cardiac function was analyzed by echocardiography on day 11. Results Here we show that inhibition of XO by oxypurinol significantly reduces wasting of the heart and preserves cardiac function. LVEF was higher in tumour-bearing rats treated with 4 mg/kg/d (61 ± 4{\%}) or 40 mg/kg/d (64 ± 5{\%}) oxypurinol vs placebo (51 ± 3{\%}, both p <0.05). Fractional shortening was improved by 4 mg/kg/d (43 ± 3{\%}) oxypurinol vs placebo (30 ± 2, p <0.05), while 40 mg/kg/d oxypurinol (41 ± 5{\%}) did not reach statistical significance. Cardiac output was increased in the 4 mg/kg/d dose only (71 ± 11 mL/min vs placebo 38 ± 4 mL/min, p <0.01). Conclusion Inhibition of XO with oxypurinol has beneficial effects on cardiac mass and function in a rat model of severe cancer cachexia, suggesting that XO might be a viable drug target in cancer cachexia.",
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