Protective effect of diindolylmethane-enriched dietary cabbage against doxorubicin-induced cardiotoxicity in mice

Chemotherapy with doxorubicin (Dox) can lead to cardiotoxic effects, presenting a major complication in cancer therapy. Diindolylmethane (DIM), derived from cruciferous vegetables like cabbage, exhibits numerous health benefits. However, its clinical application is limited because of low bioavailability and suboptimal natural concentra-
tions in dietary sources. To address this limitation, we developed a processing meth-odology, specifically fermentation and boiling, to enhance DIM levels in cabbage.
High-performance liquid chromatography (HPLC) analysis revealed a threefold DIM
increase in fermented cabbage and a substantial ninefold increase in fermented-
boiled cabbage compared to raw cabbage. To evaluate the clinical implications, we
formulated a DIM-enriched diet and administered it to mice undergoing Dox treat-
ment. Our in vivo results revealed that Dox treatment led to cardiotoxicity, mani-
fested by changes in body and heart weight, increased mortality, and severe
myocardial tissue degeneration. Dietary administration of the DIM-enriched diet
enhanced antioxidant defenses and inhibited apoptosis in the cardiac tissue by inter-
fering with mitoptosis and increasing antioxidant enzyme expression. Interestingly,
we found that the DIM-enriched diet inhibited the nuclear translocation of NF-kB in
cardiac tissue, thereby downregulating the expression of inflammatory mediators
such as TNF-α and IL-6. Further, the DIM-enriched diet significantly reduced serum
cardiac injury markers elevated by Dox treatment. These results suggest that the
DIM-enriched cabbage diet can serve as a complementary dietary intervention for
cancer patients undergoing chemotherapy. Further, our research highlights the role
of plant-based diets in reducing treatment side effects and improving the quality of
life for cancer patients.