title: Carcinine has 4-hydroxynonenal scavenging property and neuroprotective effect in mouse retina.
abstract: OBJECTIVE
  Oxidative stress induces retinal damage and contributes to vision loss in progressive retinopathies. Carcinine (β-alanyl-histamine) is a natural imidazole-containing peptide derivative with antioxidant activity. It is predicted to scavenge 4-hydroxynonenal (4-HNE), a toxic product of lipid oxidation. The aim of this study was to confirm the 4-HNE scavenging effect and evaluate the neuroprotective effect of carcinine in mouse retina subjected to oxidative stress.
  
  
  METHODS
  HPLC coupled with mass spectrometry was used to analyze carcinine and 4-HNE-carcinine adduct. Protection of retinal proteins from modification by 4-HNE was tested by incubating carcinine with retinal protein extract and 4-HNE. Modified retinal proteins were quantified by dot-blot analysis. Mice were treated with carcinine (intravitreal injection and gavage) and exposed to bright light to induce oxidative damage in the retina. Photoreceptor degeneration was measured by histology and electroretinography. Retinal levels of retinol dehydrogenase 12 (RDH12) were measured by immunoblot analysis, after exposure to bright light and in retinal explants after exposure to 4-HNE.
  
  
  RESULTS
  The ability of carcinine to form an adduct with 4-HNE, as well as to prevent and even reverse the adduction of retinal proteins by the toxic aldehyde was demonstrated in vitro. Carcinine, administered by intravitreal injection or gavage, strongly protected mouse retina against light-induced photoreceptor degeneration and had a protective effect on RHD12, a protein found specifically in photoreceptor cells.
  
  
  CONCLUSIONS
  This study suggests that carcinine can be administered noninvasively to efficiently protect photoreceptor cells from oxidative damage. Carcinine could be administered daily to prevent vision loss in progressive retinopathies.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Lea D
authors.initials: LD
authors.lastname: Marchette
authors.forename: Huaiwen
authors.initials: H
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Mark A
authors.initials: MA
authors.lastname: Babizhayev
authors.forename: Anne
authors.initials: A
authors.lastname: Kasus-Jacobi
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D041702:BALB 3T3 Cells; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004596:Electroretinography; D005136:Eye Proteins / Q000187:drug effects* / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D012160:Retina / Q000187:drug effects*; D012162:Retinal Degeneration / Q000473:pathology*; D050697:Retinal Dehydrogenase / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000447:Aldehydes; D005136:Eye Proteins; D018696:Neuroprotective Agents; D002336:Carnosine; D050697:Retinal Dehydrogenase; C027576:4-hydroxy-2-nonenal; C015055:carcinine