title: The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany; Center for Cardiovascular Research, Charite Medical School, Berlin, Germany; Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address: jochen.springer@charite.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
authors.forename: Anika
authors.initials: A
authors.lastname: Tschirner
authors.forename: Kai
authors.initials: K
authors.lastname: Hartman
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
mesh_terms: D000818:Animals; D002100:Cachexia / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D010117:Oxypurinol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D014969:Xanthine Oxidase; D010117:Oxypurinol
keywords: Cancer cachexia; Cardiac function; Heart; Oxypurinol; Uric acid; Xanthine oxidase