Cyclosporine A-induced changes to erythrocyte redox balance is time course-dependent

Basic Clin Pharmacol Toxicol. 2005 Sep;97(3):135-40. doi: 10.1111/j.1742-7843.2005.pto_973120.x.

Abstract

Cyclosporine A-treated transplant recipients develop pronounced cardiovascular disease and have increased oxidative stress and altered antioxidant capacity in erythrocytes and plasma. These experiments investigated the time-course of cyclosporine A-induced changes to redox balance in plasma and erythrocytes. Rats were randomly assigned to either a control or cyclosporine A-treated group. Treatment animals received 25 mg/kg of cyclosporine A via intraperitoneal injection for either 7 days or a single dose. Control rats were injected with the same volume of the vehicle. Three hours after the final injections, plasma was analysed for total antioxidant status, alpha-tocopherol, malondialdehyde, and creatinine. Erythrocytes were analysed for reduced glutathione (GSH), alpha-tocopherol, methaemoglobin, malondialdehyde, and the activities of superoxide dismutase, catalase, GSH peroxidase, and glucose-6-phosphate dehydrogenase (G6PD). Cyclosporine A administration for 7 days resulted in a significant increase (P<0.05) in plasma malondialdehyde, methaemoglobin, and superoxide dismutase and catalase activities. There was a significant decrease (P<0.05) in erythrocyte GSH concentration and G6PD activity in cyclosporine A animals. There were no significant differences (P>0.05) between groups following a single dose of cyclosporine A in any of the measures. In summary, cyclosporine A alters erythrocyte redox balance after 7 days administration, but not after a single dose.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Body Weight / drug effects
  • Catalase / blood
  • Cyclosporine / toxicity*
  • Erythrocytes / drug effects*
  • Erythrocytes / enzymology
  • Erythrocytes / metabolism
  • Glutathione Peroxidase / blood
  • Hemoglobins / metabolism
  • Immunosuppressive Agents / toxicity*
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / blood
  • Methemoglobin / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / blood

Substances

  • Antioxidants
  • Hemoglobins
  • Immunosuppressive Agents
  • Malondialdehyde
  • Cyclosporine
  • Methemoglobin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase