Possible Mechanisms of the Prevention of Doxorubicin Toxicity by Cichoric Acid-Antioxidant Nutrient

Nutrients. 2018 Jan 5;10(1):44. doi: 10.3390/nu10010044.

Abstract

Skin is the largest organ in the human body, and which protects organism against unfavorable external factors e.g., chemicals, environment pollutants, allergens, microorganisms, and it plays a crucial role in maintaining general homeostasis. It is also an important target of oxidative stress due to the activity of oxygen reactive species (ROS), which are constantly generated in the fibroblasts in response to exogenous or endogenous prooxidant agents. An example of such compound with proved prooxidant activity is Doxorubicin (DOX), which is an effective anticancer agent belongs in anthracycline antibiotic group. Increasingly frequent implementation of various strategies to reduce undesirable DOX side effects was observed. Very promising results come from the combination of DOX with dietary antioxidants from the polyphenol group of compounds, such as cichoric acid (CA) in order to lower oxidative stress level. The aim of this work was to evaluate the influence of CA combined with DOX on the oxidative stress parameters in fibroblasts, which constitute the main cells in human skin. We also wanted to examine anti-apoptotic activity of CA in fibroblasts treated with selected concentrations of DOX. Results obtained from the combination of DOX with CA revealed that CA exhibits cytoprotective activity against DOX-induced damage by lowering oxidative stress level and by inhibiting apoptosis. The present finding may indicate that CA may serve as antioxidative and anti-apoptotic agent, active against DOX-induced damage.

Keywords: cichoric acid; doxorubicin; fibroblasts; oxidative stress; skin.

MeSH terms

  • Antibiotics, Antineoplastic / toxicity*
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caffeic Acids / pharmacology*
  • Caspases / metabolism
  • Cell Line
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Doxorubicin / toxicity*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Glutathione / metabolism
  • Humans
  • Lipid Peroxidation / drug effects
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Succinates / pharmacology*
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Time Factors

Substances

  • Antibiotics, Antineoplastic
  • Antioxidants
  • Caffeic Acids
  • Reactive Oxygen Species
  • Succinates
  • Thiobarbituric Acid Reactive Substances
  • Doxorubicin
  • Caspases
  • Glutathione
  • chicoric acid