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

Author:

Natesh Jagadish12,Mondal Priya12,Penta Dhanamjai12,Mukhlis Yahya12,Haware Devendra Jaganath23,Meeran Syed Musthapa12ORCID

Affiliation:

1. Department of Biochemistry CSIR‐Central Food Technological Research Institute Mysore 570020 India

2. Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 201002 India

3. Food Safety & Analytical Quality Control Laboratory CSIR‐Central Food Technological Research Institute Mysore 570020 India

Abstract

AbstractChemotherapy 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 concentrations in dietary sources. To address this limitation, we developed a processing methodology, 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 treatment. Our in vivo results revealed that Dox treatment led to cardiotoxicity, manifested 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 interfering 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.

Funder

Central Food Technological Research Institute, Council of Scientific and Industrial Research

Publisher

Wiley

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