Effects of emodin treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion injury in rat hearts: single versus multiple doses and gender difference

Life Sci. 2005 Oct 14;77(22):2770-82. doi: 10.1016/j.lfs.2005.03.027.

Abstract

Effects of emodin (EMD) treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion (I-R) injury were examined in male and female rat hearts. Isolated-perfused hearts prepared from female rats were less susceptible to I-R injury than those of male rats. I-R caused significant decreases in ATP generation capacity and reduced glutathione (GSH) and alpha-tocopherol (alpha-TOC) levels as well as glutathione reductase, Se-glutathione peroxidase and Mn-superoxide dismutase (SOD) activities. The lower susceptibility of female hearts to myocardial I-R injury was associated with higher levels of GSH and alpha-TOC as well as activity of SOD than those of male hearts. EMD treatment at 3 daily doses (0.6 or 1.2 mmol/kg) could enhance myocardial mitochondrial ATP generation capacity and antioxidant components in both male and female rat hearts, but it only significantly protected against I-R injury in female hearts. Treatment with a single dose of EMD invariably enhanced mitochondrial antioxidant components and protected against I-R injury in both male and female hearts. The gender-dependent effect of EMD treatment at multiple doses may be related to the differential antioxidant response in the myocardium and/or induction of drug metabolizing enzymes in the liver.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Analysis of Variance
  • Animals
  • Antioxidants / metabolism*
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Emodin / pharmacology*
  • Emodin / therapeutic use*
  • Female
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Heart / drug effects*
  • Male
  • Mitochondria / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Sex Factors
  • Superoxide Dismutase / metabolism
  • alpha-Tocopherol / metabolism

Substances

  • Antioxidants
  • Adenosine Triphosphate
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione
  • alpha-Tocopherol
  • Emodin