Therapeutic role of lactoferrin against doxorubicin-induced cardiotoxicity in Wistar rats.

INTRODUCTION AND

OBJECTIVES

Doxorubicin-associated cardiotoxicity is an alarming concern as it limits the use of anticancer drugs in a clinical setting. The objective of this study was to test the therapeutic role of lactoferrin in preventing doxorubicin-induced cardiotoxicity and thus address this severe side effect of chemotherapy.

METHODS

Wistar rats received vehicle or DOX (2.5 mg/kg, i.p.) three times a week for two weeks and lactoferrin (50 mg/kg, i.p.) for 15 days (i.e., from day 1 to day 15 along with DOX). Changes in body weight, heart weight, and cardiotoxicity markers (blood pressure, LDH, CK-MB, and cardiac troponin I) were evaluated. Furthermore, all the animals were evaluated for the modulation of inflammatory markers (BNP, IL-6, CRP, and TNF-α), histopathological changes in heart tissue, and oxidant and antioxidant status.

RESULTS

Doxorubicin significantly (p<0.01) reduced body weight and increased the levels of cardiotoxic biomarkers (blood pressure, LDH, CK-MB, BNP, cardiac troponin I, IL-6, CRP, and TNF-α), whereas these effects were reversed in lactoferrin-treated animals. Histopathologically, heart tissue in the doxorubicin-treated group was found to contain muddled myocardial fibers, dilated blood capillaries, and necrosis in muscle fibers; however, these abnormalities were restored to normal levels in the lactoferrin therapy group. Finally, lactoferrin significantly (p<0.05) increased the levels of antioxidative enzymes (glutathione and SOD) and decreased the levels of oxidants (NO) compared with those in the untreated cardiotoxicity group.

CONCLUSION

The present study revealed the immunomodulatory, antioxidative potential of lactoferrin in restoring normal heart tissue, thereby mitigating the effects of doxorubicin-induced cardiotoxicity.