Resveratrol and adipose-derived mesenchymal stem cells are effective in the prevention and treatment of doxorubicin cardiotoxicity in rats.
Anthracyclines can cause severe cardiac toxicity leading to heart failure. The aim of this study was to determine the effects of cardioprotective polyphenolic compound resveratrol (RES) and adipose-derived mesenchymal stem cells (ADMSCs) on cardiac tissue of rats treated with doxorubicin (DOX). Forty-two female and three male Wistar-Albino rats were included in the study. The study groups and the control groups were as follows: Group I: DOX; Group II: DOX + RES; Group III: DOX + ADMSCs; Group IV: DOX + RES + ADMSCs; Group V: Sham operation; and Group VI: normal saline. ADMSCs obtained from male rats were defined with stem cell markers [CD11b/c(-), CD45(-), CD90(+), CD44(+), and CD49(+)]. DOX 12 mg/kg intraperitoneally (i.p.) was injected as a single dose in female rats. Resveratrol 100 mg/kg was injected three times i.p. in Groups II and IV. ADMSCs 2 × 10(6) cells/kg/dose were labeled with bromodeoxyuridine (BrdU) and injected i.p. for a total of three times in Groups III and IV. When the study was terminated after 4 weeks, the beating hearts were connected to a Langendorff setup and records were obtained for 30 minutes. Histopathological, immunhistochemical, and immunofluorescent examination with H&E, Troponin I, and BrdU stains were also performed. Also, ADMSCs were demonstrated in the myocardium of transplanted rats. Left ventricle functions and myocardial histology demonstrated significant impairment in DOX only group compared to groups with ADMSCs (P < .05). We suggest that RES and ADMSCs were successful in the prevention and treatment of the doxorubicin cardiomyopathy in rats. The hypothetical mechanisms of regeneration are multiple, including cell differentiation and autocrine/paracrine effects of ADMSCs.
Center of Cell Research and Genetic Diagnosis, Dışkapı Yıldırım Beyazıt Research Hospital, Ankara, Turkey. fgpinarli@gazi.edu.tr
Ferda Alpaslan
FA
Pınarlı
Nilüfer N
NN
Turan
Faruk Güçlü
FG
Pınarlı
Arzu
A
Okur
Devrim
D
Sönmez
Tulga
T
Ulus
Aynur
A
Oğuz
Ceyda
C
Karadeniz
Tuncay
T
Delibaşı
D000273:Adipose Tissue; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D049109:Cell Proliferation; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D013267:Stilbenes; D004317:Doxorubicin; D000077185:Resveratrol