Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats

J Pharm Pharmacol. 2011 Dec;63(12):1566-71. doi: 10.1111/j.2042-7158.2011.01359.x. Epub 2011 Sep 28.

Abstract

Objectives: This study aimed to investigate the antioxidant and anti-inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)-induced hepatorenal oxidative damage in rats.

Methods: Following a single dose of methotrexate (20 mg/kg), either vehicle (MTX group) or CAPE (10 µmol/kg, MTX + CAPE group) was administered for five days. In other rats, vehicle (control group) or CAPE was injected for five days, following a single dose of saline injection. After decapitation of the rats, trunk blood was obtained, and the liver and kidney tissues were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and sodium potassium-adenosine triphosphatase (Na(+)/K(+) -ATPase) activity. TNF-α and IL-1β levels were measured in the blood.

Key findings: Methotrexate administration increased the tissue MDA levels, MPO activity and decreased GSH levels and Na(+)/K(+) -ATPase activity, while these alterations were reversed in the CAPE-treated MTX group. Elevated TNF-α and IL-1β levels were also reduced with CAPE treatment.

Conclusions: The results of this study revealed that CAPE, through its anti-inflammatory and antioxidant actions, alleviates methotrexate-induced oxidative damage, which suggests that CAPE may be of therapeutic benefit when used with methotrexate.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity*
  • Caffeic Acids / pharmacology*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Female
  • Glutathione / metabolism
  • Interleukin-1beta / metabolism
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Male
  • Malondialdehyde / metabolism
  • Methotrexate / antagonists & inhibitors*
  • Methotrexate / toxicity
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Rats
  • Rats, Wistar
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antimetabolites, Antineoplastic
  • Caffeic Acids
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Peroxidase
  • Sodium-Potassium-Exchanging ATPase
  • caffeic acid phenethyl ester
  • Glutathione
  • Phenylethyl Alcohol
  • Methotrexate