The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy.
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.
['Springer|Jochen|J|', 'Tschirner|Anika|A|', 'Hartman|Kai|K|', 'von Haehling|Stephan|S|', 'Anker|Stefan D|SD|', 'Doehner|Wolfram|W|']
D000818:Animals D002100:Cachexia D009202:Cardiomyopathies D008113:Liver Neoplasms D008114:Liver Neoplasms, Experimental D008297:Male D010117:Oxypurinol D051381:Rats D017208:Rats, Wistar D014969:Xanthine Oxidase
Xanthine oxidase Oxypurinol Cancer cachexia Heart Cardiac function Uric acid