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.