Monensin, a well-known ionophore antibiotic, may cause severe damage in myocardial cells. We investigated whether IRFI 042, a new analogue of vitamin E, may block lipid peroxidation in myocardial cells and in turn protect against monensin toxicity. Monensin toxicity was induced by repeated daily administration of the ionophore antibiotic (150 mg/kg/day for 7 days). Sham animals received by oral gavages only a saline solution and were used as controls. All animals were randomized to receive concomitantly by oral gavages IRFI 042 (20 mg/kg) or its vehicle. The experiment lasted 8 days. Survival rate, heart lipid peroxidation, studied by means of thiobarbituric acid-reactive substances (TBARs) levels, cardiac expression of endothelial nitric oxide (e-NOS) and histological analysis of the heart were performed. Monensin administration caused a decrease in survival rate. Mortality appeared following the second monensin injection and at day 7 caused a survival rate of 20%. Thereafter, no further mortality was observed. IRFI 042 administration improved survival rate. Injection of the ionophore antibiotic resulted in a marked cardiac lipid peroxidation and in a significant reduction in cardiac e-NOS message and protein expression. IRFI 042 decreased heart TBARs levels (Monensin + vehicle = 6.5 +/- 0.8 nmol/mg; Monensin + IRFI 042 = 3.2 +/- 1.1 nmol/mg; P < 0.001) and increased e-NOS message and protein expression. Histological analysis showed that IRFI 042 improved myocardial cells damage and enhanced the depressed e-NOS expression in chick heart samples following monensin administration. Our data suggest that IRFI 042 is a promising drug to reduce monensin cardio-toxicity in chicks.