The Mitigating Role of Transresveratrol Against Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients via Modulating Mitochondrial Gene Expression: A Randomized Controlled Trial

Abstract

Background: Increased awareness of the adverse cardiac effects of chemotherapeutic agents makes the paradigm of care has shifted to a double hit goal of increasing cancer survival with cardiac protection. Breast cancer (BC) patients treated with Doxorubicin (DOX, Adriamycin®) usually develop cardiotoxicity. Therefore, our trial aimed to investigate the cardioprotective role of the polyphenolic transresveratrol (Transresv) supplement with Adriamycin-Cytoxan (AC) chemotherapy protocol to mitigate DOX-induced cardiotoxicity (DIC).

Methods: This study is a randomized controlled clinical trial (RCT) recruiting 54 BC patients who were randomly allocated into two equal groups. A control group (AC group) received four cycles of AC chemotherapy, each of which was three weeks apart in a dose of 60 mg/m2 Adriamycin with 600 mg/m2 Cytoxan. An intervention group (AC/Transresv group) received the same AC protocol with 150 mg/day Transresv orally. Baseline characteristics were analyzed. Serum cTnI, CK-MB, LVEF, mitochondrial gene expression of NADH dehydrogenase, cytochrome c oxidase I, II, III subunits, CRP, MDA, and t-SOD were assessed pre and post intervention.

Results: There was no significant difference between AC and AC/Transresv groups concerning baseline characteristics. AC group revealed a significant increase in cTnI, CRP, and MDA with a decrease in LVEF, t-SOD, beside down regulation of mitochondrial genes with a non-significant change in CK-MB after 4th AC cycle compared to baseline values. AC/Transresv group exhibited a significant improvement in almost all parameters compared to AC group.

Conclusion: Transresv supplementation with AC protocol alleviates DIC in the BC patients via modulating diverse signaling pathways and targeting mitochondrial biogenesis.