The effect of lithospermic acid, an antioxidant, on development of diabetic retinopathy in spontaneously obese diabetic rats

PLoS One. 2014 Jun 6;9(6):e98232. doi: 10.1371/journal.pone.0098232. eCollection 2014.

Abstract

Background: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.

Methods and findings: LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls.

Conclusions: Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Antioxidants / therapeutic use*
  • Benzofurans / therapeutic use*
  • C-Reactive Protein / metabolism
  • Chemokine CCL2 / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Depsides / therapeutic use*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / prevention & control*
  • Glucose / metabolism
  • Glucose Intolerance / drug therapy
  • Insulin Resistance
  • Male
  • Obesity / complications
  • Rats
  • Rats, Long-Evans
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antioxidants
  • Benzofurans
  • Chemokine CCL2
  • Depsides
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • lithospermic acid
  • 8-Hydroxy-2'-Deoxyguanosine
  • C-Reactive Protein
  • Deoxyguanosine
  • Glucose

Grants and funding

This work was supported by the Korean Diabetes Association (2009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.