In Vivo and In Vitro Protective Effects of Rosmarinic Acid against Doxorubicin-Induced Cardiotoxicity

Nutr Cancer. 2022;74(2):747-760. doi: 10.1080/01635581.2021.1931362. Epub 2021 Jun 4.


Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects. This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments. Male rats were randomized on 7 groups: (1) control, (2) DOX (2 mg/kg, per 48 h, 12d, i.p), (3) RA (40 mg/kg, 12d, i.p.), (4-6) RA (10, 20, 40 mg/kg, 16d, i.p.)+ DOX, (7) Vitamin E (200 mg/kg, per 48 h, 16d, i.p.) + DOX and then indices of cardiac function were estimated. Also, DOX and rosmarinic acid effects were examined on MCF7 cells (breast cancer cells line) to clarify that both cardiotoxicity and anticancer effects were analyzed. DOX increased heart to body weight ratio, RRI, QA, STI, QRS duration and voltage, attenuated HR, blood pressure, Max dP/dt, Min dP/dt, LVDP, enhanced MDA, declined GSH amount, and caused fibrosis and necrosis in cardiac tissue. Administration of RA ameliorated the toxic effects of DOX. In vitro studies showed that RA did not affect the cytotoxic effect of DOX. RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.

Publication types

  • Randomized Controlled Trial, Veterinary
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Cardiotoxicity* / drug therapy
  • Cardiotoxicity* / etiology
  • Cardiotoxicity* / prevention & control
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use
  • Depsides / pharmacology
  • Depsides / therapeutic use
  • Doxorubicin* / toxicity
  • Male
  • Oxidative Stress
  • Rats


  • Antibiotics, Antineoplastic
  • Cinnamates
  • Depsides
  • Doxorubicin
  • rosmarinic acid