Doxorubicin is a chemotherapeutic agent that is widely used in the treatment of malignancies. However, its clinical application is limited, mainly because of its cardiotoxic effects. Berberine is a form of traditional Chinese medicine and has a wide range of pharmacological properties and a proposed role in combating many cardiovascular diseases.Aim
This work aimed to investigate novel mechanisms underlying doxorubicin-induced cardiotoxicity and to evaluate the potential protective role of berberine.Materials and methods
Thirty-six adult male albino rats were divided into four equal groups: the control group, the berberine-treated group (60 mg/kg), the doxorubicin-treated group (2.5 mg/kg), and both doxorubicin and berberine-treated group. Animals were intraperitoneally injected every other day for 2 weeks. Specimens from the cardiac muscle were processed for light and electron microscopy. Immunohistochemical study was carried out using antibodies against Toll-like receptor (TLR2), nuclear factor-kB (NF-kB), and activated caspase-3.Results
Specimens from doxorubicin-treated animals showed focal disruption of cardiomyocytes with nuclear alteration and vacuolated sarcoplasm. Some mononuclear cells, dilated congested blood vessels, and abundant collagen fibre deposition were also observed. Ultrastructurally, irregular indented nuclei, focal lysis of myofibrils, loss of normal cross striations, swelling of mitochondria, and distortion of intercalated disks were observed. Immunohistochemical study showed a significant increase in TLR2, NF-kB, and activated caspase-3 immunoreaction. In contrast, minimal changes were observed in rats treated concomitantly with both doxorubicin and berberine, with a nonsignificant increase in the immunoreactions.Conclusion
Doxorubicin induced structural changes in the cardiac muscle of adult albino rats, which could be ameliorated by concomitant treatment with berberine.