IL-10 mitigates doxorubicin induced cardiotoxicity

Background: The main pathophysiologic effect of do-xorubicin induced cardiotoxicity underlines the role of inflammatory response triggered by anthracycline ma-nifested by proinflammatory cytokines expression and deficiency of principal antiinflammatory interleukins, IL-4 and IL-10.
Objective: the in vitro evaluation of IL-10 effect on do-xorubicin induced cardiotoxicity.
Material and Methods: Doxorubicin (Dx) has been administered in rats i/peritoneally 2 times per week in a cardiotoxic cumulative dose, 10 mg/kg – series 1. In the series 2, animals received during Dx action IL-10 by using a special mini-pump of infusion (50 μg/kg/day during 7 days). The series 3 was formed by control rats. At 10th day animals have been euthanized and isolated heart was perfused in izovolumic regimen (Langen-dorff ’ method) or exterior working regimen (Neely-Rovetto method). The left ventricle (VS) parameters were assayed using the system of functional indices re-cording in real time Bio-Shell (Germany).
Results: Dx administration in the 1st series led to sig-nificant decrease of cardiac output and Veragut’ in-dex by 16.8 and 14.9% respectively comparatively to control, and elevation of LV end-diastolic pressure by 25.7% (p<0.01). The inotropic response of isolated heart on endothelin-1 (ET-1) action was negative, such as LV systolic pressure (LVSP) reduced by 9.4% followed by the cardiac output diminution by 10.4% vs. basal (premedication) level, whilst in control a positive inotropic effect was attested – LVSP raised by 12.3%. Moreover, coronary reserve inherent to acetylcholi-ne action was under the control level: 20.3±3.2% vs. 32.6±3.9% (p<0.01). IL-10 administration notably li-mited Dx induced cardiac dysfunction. Thus, cardiac output, Veragut’ index and LVSP elevated comparated with series 1 indices, and a significant (p<0.05) incre-ment was estimated in the tests with resistance effort: 18.1±2.5 vs. 13.8±2.4 ml/min; 7832±890 vs. 6940±810 1/sec; 139.4±13.2 vs. 118.6±13.7 mm Hg. Likewise, IL-10 improved myocardium inotropism, and LVSP in-creased during ET-1 action by 7.3%. Positive inotropic effect was associated with cardiac output enhancement by 8,2%. Importantly, coronary flow on acetylcholine action increased by 28.7% (p<0.05 vs. series 1).
Conclusion: IL-10 action limits the Dx induced car-diotoxicity, a benefit manifested by significant higher values of cardiac output, Veragut’ index, LVSP, coro-nary functional reserve, as well as by appearance of the positive inotropic effect on ET-1 action.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)