Farnesol Protects against Cardiotoxicity Caused by Doxorubicin-Induced Stress, Inflammation, and Cell Death: An In Vivo Study in Wistar Rats

Molecules. 2022 Dec 6;27(23):8589. doi: 10.3390/molecules27238589.

Abstract

Doxorubicin (DOXO) is an antineoplastic drug that is used extensively in managing multiple cancer types. However, DOXO-induced cardiotoxicity is a limiting factor for its widespread use and considerably affects patients' quality of life. Farnesol (FSN) is a sesquiterpene with antioxidant, anti-inflammatory, and anti-tumor properties. Thus, the current study explored the cardioprotective effect of FSN against DOXO-induced cardiotoxicity. In this study, male Wistar rats were randomly divided into five groups (n = 7) and treated for 14 days. Group I (Control): normal saline, p.o. daily for 14 days; Group II (TOXIC): DOXO 2.4 mg/kg, i.p, thrice weekly for 14 days; Group III: FSN 100 mg/kg, p.o. daily for 14 days + DOXO similar to Group II; Group IV: FSN 200 mg/kg, p.o. daily for 14 days + DOXO similar to Group II; Group V (Standard): nifedipine 10 mg/kg, p.o. daily for 14 days + DOXO similar to Group II. At the end of the study, animals were weighed, blood was collected, and heart-weight was measured. The cardiac tissue was used to estimate biochemical markers and for histopathological studies. The observed results revealed that the FSN-treated group rats showed decrease in heart weight and heart weight/body weight ratio, reversed the oxidative stress, cardiac-specific injury markers, proinflammatory and proapoptotic markers and histopathological aberrations towards normal, and showed cardioprotection. In summary, the FSN reduces cardiac injuries caused by DOXO via its antioxidant, anti-inflammatory, and anti-apoptotic potential. However, more detailed mechanism-based studies are needed to bring this drug into clinical use.

Keywords: NF-kB; cardioprotection; caspase-3; farnesol; inflammation; reactive oxygen species.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cardiotoxicity / drug therapy
  • Cardiotoxicity / etiology
  • Cardiotoxicity / prevention & control
  • Cell Death
  • Doxorubicin / pharmacology
  • Farnesol* / pharmacology
  • Farnesol* / therapeutic use
  • Inflammation / metabolism
  • Male
  • Myocytes, Cardiac
  • Oxidative Stress
  • Quality of Life*
  • Rats
  • Rats, Wistar

Substances

  • Farnesol
  • Doxorubicin
  • Antioxidants

Grants and funding

The authors are thankful to the Deanship of Scientific Research at Najran University, Najran, Kingdom of Saudi Arabia for funding this work under the Research Collaboration funding program grant No. NU/RG/MRC/11/2.