Ability of <i>N</i>‐acetylcarnosine to protect lens crystallins from oxidation and oxidative damage by radical probe mass spectrometry (RP‐MS)

Ha, Ji-won; Schwahn, Alexander B.; Downard, Kevin M.

doi:10.1002/rcm.4720

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…The dipeptide N-acetyl carnosine was reported to improve visual acuity and glare sensitivity in human subjects diagnosed with various stages of cataract disease [102]. It is available as a topical ophthalmic supplement, despite lacking US FDA approval, and there is conflicting evidence for its function [103]. Varma and colleagues found that caffeine maintained the transparency of lenses from selenite-treated animals [104] and reduced both lens opacity and damage to ion pumps caused by UV-B radiation [105].…”

Section: Prevention or Retardation Of Cataract Diseasementioning

confidence: 99%

Protein misfolding and aggregation in cataract disease and prospects for prevention

Moreau

King

2012

Trends in Molecular Medicine

373

302

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The transparency of the eye lens depends on maintaining the native tertiary structures and solubility of the lens crystallin proteins over a lifetime. Cataract, the leading cause of blindness worldwide, is caused by protein aggregation within the protected lens environment. With age, covalent protein damage accumulates through pathways thought to include UV radiation, oxidation, deamidation, and truncations. Experiments suggest that the resulting protein destabilization leads to partially unfolded, aggregation-prone intermediates and the formation of insoluble, light-scattering protein aggregates. These aggregates either include or overwhelm the protein chaperone content of the lens. Here we review the causes of cataracts and non-surgical methods being investigated to inhibit or delay cataract development, including natural product-based therapies, modulators of oxidation, and protein aggregation inhibitors.

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Section: Prevention or Retardation Of Cataract Diseasementioning

confidence: 99%

Protein misfolding and aggregation in cataract disease and prospects for prevention

Moreau

King

2012

Trends in Molecular Medicine

373

302

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“…22 On the other hand, higher spray voltage will result in more vigorous CD, based on which Downard's group have done intensive proteomics-related research. [31][32][33] Therefore, the results indicated that a more sever CD through raising spray voltage or using metal spray emitter facilitated the formation of Mc À ions.…”

Section: Effect Of Experimental Parameters On Dcbq Reductionmentioning

confidence: 86%

Corona discharge-induced reduction of quinones in negative electrospray ionization mass spectrometry

et al. 2017

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“…Another publication of the Australian scientists demonstrates further misunderstanding of N‐acetylcarnosine ophthalmology concept 65. The authors applied radical probe‐mass spectrometry (RP‐MS) based on protein footprinting studies to investigate the effectiveness of the antioxidant N‐acetylcarnosine in preventing oxidative damage to lens crystallins present in the eye of mammals.…”

Section: Discussionmentioning

confidence: 99%

“…Another publication of the Australian scientists demonstrates further misunderstanding of N-acetylcarnosine ophthalmology concept. [65] The authors applied radical probe-mass spectrometry (RP-MS) based on protein footprinting studies to investigate the effectiveness of the antioxidant N-acetylcarnosine in preventing oxidative damage to lens crystallins present in the eye of mammals. No evidence was found to suggest that the antioxidant had any significant direct effect on reducing the levels of oxidation within the most abundant lens crystallins, α and β-crystallin, at the molecular level at increasing concentrations of N-acetylcarnosine.…”

Section: Discussionmentioning

confidence: 99%

Bioactivation antioxidant and transglycating properties of N‐acetylcarnosine autoinduction prodrug of a dipeptide L‐carnosine in mucoadhesive drug delivery eye‐drop formulation: powerful eye health application technique and therapeutic platform

Babizhayev

2011

Drug Testing and Analysis

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A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of the study document that the therapeutic benefit in clinical trials is associated with the bioactivation universal antioxidant and transglycating properties of N-acetylcarnosine acting as the ophthalmic prodrug of L-carnosine, and depends on the nature of the specific drug delivery lubricant eye-drop formulation applied as the topical solution. The research highlights findings in N-acetylcarnosine prodrug activation, transport mechanisms, drug-to-drug interactions, and formulations in order to unlock the optimization of complicated ocular pharmacology of N-acetylcarnosine. Patented N-acetylcarnosine lubricant eye-drop formula was marketed as numerous human biological brands reaching important distribution networks on over 550 000 bottles sold. Nature Does Nothing Uselessly. -Aristotle

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Ability of N‐acetylcarnosine to protect lens crystallins from oxidation and oxidative damage by radical probe mass spectrometry (RP‐MS)

Cited by 9 publications

References 37 publications

Protein misfolding and aggregation in cataract disease and prospects for prevention

Protein misfolding and aggregation in cataract disease and prospects for prevention

Corona discharge-induced reduction of quinones in negative electrospray ionization mass spectrometry

Bioactivation antioxidant and transglycating properties of N‐acetylcarnosine autoinduction prodrug of a dipeptide L‐carnosine in mucoadhesive drug delivery eye‐drop formulation: powerful eye health application technique and therapeutic platform

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