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Anne Kasus-Jacobi, Huaiwen Wang, Lea D. Marchette; Carcinine Has Antioxidant and 4-Hydroxynonenal Scavenging Properties Offering Strong Neuroprotection From Oxidative Damage in Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3397.
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Oxidative stress and lipid peroxidation induce retinal damage and contribute to vision loss in progressive retinopathies such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Carcinine is a naturally occurring imidazole-containing pseudopeptide with known antioxidant activity. It is also predicted to have a quenching effect on 4-hydroxynonenal (4-HNE), a highly toxic product of oxidative stress. The Aim of this study was to confirm this quenching effect and evaluate the neuroprotective efficiency of carcinine in mouse retina subjected to oxidative stress.
Retinal protein extract and 4-HNE were incubated in presence of increasing amounts of carcinine in vitro. Inhibition of adduct formation between 4-HNE and protein was measured by dot-blot analysis. Pre-formed adducts were also incubated with carcinine and reversion of 4-HNE modification was quantified. BALB/c mice were treated with carcinine by gavage and exposed to bright light to induce oxidative stress and endogenous production of 4-HNE. Protection of photoreceptors by carcinine was quantified by histology and electroretinography.
Using a combined HPLC and mass spectrometric approach, we showed that carcinine does form an adduct with 4-HNE. This quenching activity prevents and even reverses detrimental 4-HNE modification of retinal proteins. Systemic administration of carcinine led to accumulation of carcinine in the retina and to a strong neuroprotection of photoreceptor cells against light-induced oxidative damage.
Compounds with antioxidant properties neutralize reactive oxygen species before they can induce any damage, providing a first line of defense against free radicals. With combined antioxidant and 4-HNE quenching activities, carcinine offers a second line of defense by targeting secondary products of oxidative stress. This study shows that combining these activities is beneficial to protect photoreceptor cells from oxidative damage. Carcinine is a well tolerated natural product which could easily be used in chronic treatment to slow down vision loss in progressive retinopathies.
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