Abstract
Doxorubicin (DOX) is a cardiotoxic drug. To reduce the harmful effects of DOX, two plant‐derived components, including curcumin (CUR) and carvacrol (CAR), were considered. This study aimed to assess the protective effects of CUR and CAR on DOX‐induced cardiotoxicity using physiological and stereological evaluations. Male rats were randomly allocated to six groups. Group's I‐VI received phosphate‐buffered saline (PBS), CUR (100 mg kg−1 day−1), CAR (50 mg kg−1 day−1), DOX (4 mg kg−1 week−1), DOX‐CUR, and DOX‐CAR, respectively. On day 24, plasma troponin I and ECG were analyzed and the left ventricle underwent stereological assessment. The results showed a fivefold increase in troponin I in the DOX‐treated animals compared to the PBS ones. Additionally, heart rate and QRS amplitude, respectively, reduced by 18% and 31% and QT interval and QRS duration, respectively, increased by 41% and 24% in the DOX group in comparison with the PBS rats (p < .05). The total volume of the myocardium and vessels and the number of cardiomyocyte nuclei also, respectively, decreased by 30%, 45%, and 43% in the DOX group compared to the PBS animals (atrophy of the ventricular tissues, p < .01). Besides, the mean volumes of the connective tissue and cardiomyocytes, respectively, increased by 46% and 52% in the DOX group (p < .01). In the DOX‐CUR and DOX‐CAR groups, the changes were prevented extensively in comparison with the DOX group (p < .01). Co‐administration of CUR or CAR and doxorubicin for 24 days could improve the heart function and structural changes.
Highlights
The most frequent etiologies of heart failure include ischemic heart disease, hypertension, diabetes, and toxins (Kemp & Conte, 2012; Pontes et al, 2010)
Where “ΣQ−” was the total number of the counted nuclei, “ΣP” was the total number of points falling on the myocardium, “a/f” was the area of the counting frame, “h” was the height of the disector, “t” was the mean section thickness measured at different places of the section, and BA was the setting of the microtome for sectioning of the block
The results showed a fivefold increase in troponin I level in the DOX‐treated groups compared to the phosphate‐buffered saline (PBS) group
Summary
The most frequent etiologies of heart failure include ischemic heart disease, hypertension, diabetes, and toxins (e.g., alcohol and cytotoxic drugs) (Kemp & Conte, 2012; Pontes et al, 2010). Along with these toxic agents, doxorubicin (DOX) was considered in the present study. Many attempts have been made to soothe DOX side effects, including “dose optimization” and “combined therapy.”. Attempts have been made to build up a combination therapy with medicinal plants to decrease the harmful properties of DOX (Singal, Li, Kumar, Danelisen, & Iliskovic, 2000). Two components with plant origin, namely curcumin (CUR) and carvacrol (CAR), were evaluated in this study to minimize the cardiac side effects of DOX
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