Abstract
Abstract 4944
Introduction:
The clinical efficacy of doxorubicin is severely limited by its cardiotoxicity. Antioxidants represent the largest class of chemicals examined as potential protective agents and for which there is continuing interest. Dexrazoxane is the current agent used for the control of doxorubicin related cardiotoxicity. However, in large trials the incidence was reduced only by 50% (1). Vitamin E, a known antioxidant and free radical scavenger agent, has been evaluated in the past as a cardio protective drug in animal models receiving doxorubicin but contradictory conclusions regarding this effect have been reported (2, 3). We hypothesized whether Vitamin E has an effect in cardioprotection in rats receiving doxorubicin.
Design and Methods:
Three groups of 6 Rats each were used for the experiment. Group 1 received doxorubicin 1.5mg/kg intraperitoneally (IP) weekly for 9 weeks for a total cumulative dose of 13.5mg/kg. Group 2 received Vitamin E 100 IU/kg/weekly by IP injection, 48 hours prior to the doxorubicin. Group 3 received 0.5 cc of saline solution 0.9% IP weekly for 9 weeks as control group. Functional parameters including plasmatic nitric oxide (NO) levels and cardiac ejection fraction (EF) were determined on each group at the end of the experiment.
Results:
Doxorubicin treatment significantly increased plasmatic NO concentration when compared with controls (35.30 ± 5.63 mM vs. 14.72 ± 2.66 mM, n=6, P=0.016); however, in the group of rats receiving Vitamin E prior to doxorubicin, NO did not have a significant decrease (from 35.30 ± 5.63 mM to 31.77± 8.91 mM n=6, P=0.75). Regarding EF, doxorubicin treatment decreased EF significantly when compared with saline controls rats (59 ± 5.61% vs. 77 ± 3.89 %, n=6, P<0.05); however, in the group of rats receiving Vitamin E prior to doxorubicin, EF did not have a significant improvement (from 59 ± 5.61% to 69.17 ± 4.4, n=6, P=0.24).
Conclusion:
These results suggest that Vitamin E does not prevent or reduce cardiac injury in rats treated with doxorubicin. Different alternatives including other antioxidants could be explored in an attempt to decrease cardiotoxicity produced by doxorubicin and to improve the effect of the standard cardioprotective agent used Dexrazoxane. Further studies are necessary.
References:
1. Swain SM. Adult multicenter trials using dexrazoxane to protect against cardiac toxicity. Semin Onco 1998; 25 (4 Suppl 10):43-7
2. Breed JG, Zimmerman AN, Dormans JA, Pinedo HM. Failure of the antioxidant vitamin E to protect against adriamycin-induced cardiotoxicity in the rabbit. Cancer Res 1980; 40:2033-8
3. Myers CE, McGuire W, Young R. Adriamycin: amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep 1976; 60:961-2
Disclosures:
No relevant conflicts of interest to declare.
The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma
