The effect of pre-treatment with Troxerutin on myocardial fibrosis in rats with doxorubicin-induced cardiotoxicity

Background. Doxorubicin (DOX) is a highly effective anthracycline drug widely used in cancer treatment. Myocardial fibrosis, a key pathological consequence of DOX-induced cardiotoxicity, impairs cardiac function and increases the risk of heart failure. Troxerutin (TXR), a natural bioflavonoid, has shown promise in mitigating myocardial injury. This study evaluated the protective effects of TXR against DOX-induced myocardial fibrosis and expression of fibrosis markers, TGF-β and Smad3. Methods. Twenty-four male Wistar rats were randomly divided into four groups: control, TXR, DOX, and DOX+TXR. TXR was administered orally at 150 mg/kg daily for 4 weeks before treatment with DOX. DOX was injected intraperitoneally at 20 mg/kg. One week after the administration of DOX, serum lactate dehydrogenase (LDH) activity was measured to assess myocardial damage, and myocardial fibrosis was evaluated histologically using Masson's trichrome staining. Gene expression of TGF-β and Smad3 was analyzed by real-time PCR. Results. DOX significantly increased serum LDH activity and myocardial fibrosis compared to controls (P<0.01). Pre-treatment with TXR significantly reduced LDH activity and myocardial fibrosis in the DOX+TXR group compared to the DOX group (P<0.05). Additionally, TXR decreased the expression of TGF-β (P<0.05) and Smad3 (P<0.01) genes, indicating a reduction in fibrotic signaling. Conclusion. TXR shows significant potential as a preventive treatment for DOX-induced myocardial toxicity. Its ability to reduce myocardial damage and fibrosis while modulating key fibrotic signaling molecules offers a promising approach for improving cardiac outcomes following DOX therapy. Practical Implications. Troxerutin could be used as an effective preventative treatment for improving cardiovascular health in cancer patients undergoing chemotherapy with DOX.