Linoleic acid induces red blood cells and hemoglobin damage via oxidative mechanism

Int J Clin Exp Pathol. 2015 May 1;8(5):5044-52. eCollection 2015.

Abstract

Hidden blood loss typically occurs following total hip arthroplasty (THA) and total knee arthroplasty (TKA) and is thought to be related to free fatty acid (FFA). To study the effect of linoleic acid on red blood cells and to examine the pathogenesis of hidden blood loss in vivo, we generated an animal model by injecting linoleic acid into the tail veins of rats. We collected blood samples and determined red blood cell count (RBC) and levels of hemoglobin (Hb), as well as the oxidation and reducing agents in the blood, including glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), hydrogen peroxide (H2O2), and ferryl hemoglobin (Fe4+=O2-), which is generated by the oxidation of Hb. Hidden blood loss occurred when linoleic acid was administered at a concentration of 60 mmol/L; RBC and Hb levels were significantly reduced by 24 h post-injection. This was followed by erythrocyte deformation, reduced activity of GSH-PX and T-SOD, and decreased levels of H2O2. This was accompanied by an increase in ferryl species, which likely contributes to oxidative stress in vivo. Our findings suggest that linoleic acid enhances acute red blood cell injury. Hb and RBC began to increase by 72 h, potentially resulting from linoleic acid metabolism. Thus, elevated levels of linoleic acid in the blood cause acute oxidative damage to red blood cells, eventually leading to partial acute anemia. These findings highlight the pathophysiology underlying hidden blood loss.

Keywords: Linoleic acid; erythrocyte damage; free fatty acid; hidden blood loss; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / blood
  • Anemia / chemically induced*
  • Anemia / pathology
  • Animals
  • Biomarkers / blood
  • Erythrocyte Deformability / drug effects
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Erythrocytes / pathology
  • Glutathione Peroxidase / blood
  • Hemoglobins / metabolism*
  • Hydrogen Peroxide / blood
  • Injections, Intravenous
  • Linoleic Acid / administration & dosage
  • Linoleic Acid / toxicity*
  • Male
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / blood
  • Time Factors

Substances

  • Biomarkers
  • Hemoglobins
  • ferrylhemoglobin
  • Linoleic Acid
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Superoxide Dismutase