Protective Effects of Melatonin and Aminoguanidine on the Cornea in Streptozotocin-Induced Diabetic Rats

Cornea. 2008 Aug;27(7):795-801. doi: 10.1097/ICO.0b013e318169d67c.


Purpose: This study was designed to investigate the protective effect of aminoguanidine (AG) and melatonin (M) on the cornea in a streptozotocin-induced diabetic rat model.

Methods: Twenty-eight Sprague-Dawley rats were used in this study. Animals were divided into 4 groups: control (C), diabetes (D), diabetes + AG (D+AG), and diabetes + M (D+M). Diabetes was induced by 1 intraperitoneal dose of 45 mg/kg of streptozotocin (STZ). In the treatment groups, the D + AG group received AG in their water (1 g/L), and D + M rats were injected with M (10 mg/kg/d) intraperitoneally. One of the groups remained an untreated diabetic group (D group). All animals were euthanized at the end of 8 weeks. After enucleation, eyes were fixed in 10% phosphate-buffered formalin and embedded in paraffin wax. Histochemical stains were applied, and specimens were examined under a light microscope.

Results: After 8 weeks, the rats in the diabetes group had significantly lower body weight and significantly higher blood glucose levels than those of the control, D + AG, and D + M groups. Diabetes resulted in prominent edema in the stroma with interruptions in the subepithelial basement membrane. These alterations were not prominent or were absent in the D + AG and D + M groups. The mean thicknesses of the cornea, corneal epithelium, and stroma were statistically significantly different between the C and D, and D and D + AG and D + M groups (P < 0.05).

Conclusions: Long-term administration of AG and M reduced corneal injury in an STZ-induced diabetic rat model. AG and M may be potential candidates in the treatment of diabetic keratopathies. However, further studies are needed to elucidate the mechanisms of the protective effect of both molecules on diabetic corneal complications.

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / administration & dosage*
  • Blood Glucose / analysis
  • Body Weight
  • Corneal Diseases / etiology
  • Corneal Diseases / pathology
  • Corneal Diseases / prevention & control*
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Guanidines / administration & dosage*
  • Injections, Intraperitoneal
  • Melatonin / administration & dosage*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley


  • Antioxidants
  • Blood Glucose
  • Enzyme Inhibitors
  • Guanidines
  • Nitric Oxide Synthase
  • Melatonin
  • pimagedine