The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats

Hum Exp Toxicol. 2019 Jul;38(7):803-813. doi: 10.1177/0960327119842634. Epub 2019 Apr 12.

Abstract

The aim of the present study was to determine the protective and therapeutic effects of linalool (LIN) against doxorubicin (DOX)-induced cardiotoxicity in rats histologically and biochemically. In experiments, 64 male Wistar albino rats were randomly divided into eight groups ( n = 8). These groups were control (C) (0.9% saline solution), DOX (20 mg/kg DOX), LIN50 (50 mg/kg LIN), LIN100 (100 mg/kg LIN), DOX + LIN50 (20 mg/kg DOX and 50 mg/kg LIN), DOX + LIN100 (20 mg/kg DOX and 100 mg/kg LIN), LIN50 + DOX (50 mg/kg LIN and 20 mg/kg DOX), and LIN100 + DOX (100 mg/kg LIN and 20 mg/kg DOX). It was determined that necrosis and extensive inflammatory cell infiltration were observed in the DOX group. It was determined that histopathological changes significantly decreased in groups treated with LIN after DOX administration. While the caspase-3 immunostaining was highly evident in DOX group apoptotic cells ( p < 0.001, for all), the intensity of caspase-3 immunostaining in the treatment groups decreased ( p < 0.05). While DOX administration resulted in a significant increase in malondialdehyde (MDA) levels and plasma Creatine kinase (CK) and lactate dehydrogenase (LDH) levels in cardiac tissue when compared to the C groups, it was observed that DOX + LIN administration led to a significant decrease in MDA, plasma CK and LDH levels and a significant increase in glutathione (GSH), superoxide dismutase, and catalase enzyme levels. Finally, it was concluded that DOX led to heavy cardiotoxicity and DOX + LIN administration could remove cardiomyopathy symptoms.

Keywords: Doxorubicin; MDA; cardiotoxicity; caspase-3; linalool; oxidative stress.

MeSH terms

  • Acyclic Monoterpenes
  • Animals
  • Antibiotics, Antineoplastic*
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cardiotoxicity / drug therapy*
  • Cardiotoxicity / metabolism
  • Cardiotoxicity / pathology
  • Caspase 3 / metabolism
  • Creatine Kinase / metabolism
  • Doxorubicin*
  • L-Lactate Dehydrogenase / metabolism
  • Malondialdehyde / metabolism
  • Monoterpenes / pharmacology
  • Monoterpenes / therapeutic use*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Rats, Wistar

Substances

  • Acyclic Monoterpenes
  • Antibiotics, Antineoplastic
  • Cardiotonic Agents
  • Monoterpenes
  • Malondialdehyde
  • Doxorubicin
  • linalool
  • L-Lactate Dehydrogenase
  • Creatine Kinase
  • Casp3 protein, rat
  • Caspase 3