The natural histidine-containing dipeptide Nalpha-acetylcarnosine as an antioxidant for ophthalmic use

Biochemistry (Mosc). 2000 May;65(5):588-98.


The naturally occurring compound Nalpha-acetylcarnosine is proposed as a prodrug of L-carnosine that is resistant to enzymatic hydrolysis by carnosinase. Eyes of rabbits were treated with 1% Nalpha-acetylcarnosine, L-carnosine, or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse-phase analytical high performance liquid chromatography (HPLC) and thin-layer (TLC) and ion-exchange chromatographic techniques. Topical administration of pure L-carnosine to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. Nalpha-Acetylcarnosine showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing L-carnosine after l5-30 min of ocular administration of the prodrug in a series of therapeutic modalities: instillation < or = subconjunctival injection < or = ultrasound-induced phoresis. Different treatment techniques showed excellent toleration of 1%Nalpha-acetylcarnosine by the eye. Once in the aqueous humor, L-carnosine might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-l5 mM). The advantage of the ophthalmic prodrug Nalpha-acetylcarnosine and its bioactivated principle L-carnosine as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in aqueous environments. Nalpha-Acetylcarnosine is proposed for treatment of ocular disorders that have a component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, and systemic diseases).

MeSH terms

  • Administration, Topical
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Antioxidants / pharmacokinetics
  • Antioxidants / pharmacology*
  • Carnosine / administration & dosage
  • Carnosine / analogs & derivatives*
  • Carnosine / chemistry
  • Carnosine / pharmacokinetics
  • Carnosine / pharmacology
  • Chromatography, High Pressure Liquid
  • Chromatography, Ion Exchange
  • Histidine / analysis*
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Male
  • Ophthalmic Solutions*
  • Oxidative Stress
  • Rabbits


  • Antioxidants
  • Ophthalmic Solutions
  • N-acetylcarnosine
  • Histidine
  • Carnosine