Analytical and physicochemical characterisation of the senile cataract drug dipeptide β-alanyl-L-histidine (carnosine)

Abdelkader, Hamdy; Swinden, Julian; Pierscionek, Barbara K.; Alany, Raid G.

doi:10.1016/j.jpba.2015.05.025

Cited by 20 publications

(11 citation statements)

References 16 publications

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“…These indirect antioxidant effects have been reported due to possible in vitro chelating properties of copper and there might be possibilities of inhibiting the initiation of intracellular Fenton's reaction. L-Carnosine did not show any oxidation by a common oxidizing agent such as hydrogen peroxide [28]. This work is aimed at investigating possible antioxidant, antiglycation, and copper chelating effects of L-carnosine; further, this work is interested in studying the cytotoxicity of L-carnosine.…”

Section: Introductionmentioning

confidence: 99%

On the Anticataractogenic Effects of L‐Carnosine: Is It Best Described as an Antioxidant, Metal‐Chelating Agent or Glycation Inhibitor?

Abdelkader

Longman

Alany

et al. 2016

Oxidative Medicine and Cellular Longevity

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Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation.

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Section: Introductionmentioning

confidence: 99%

On the Anticataractogenic Effects of L‐Carnosine: Is It Best Described as an Antioxidant, Metal‐Chelating Agent or Glycation Inhibitor?

Abdelkader

Longman

Alany

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…We have already focused on carnosine as one such substance because it possesses various beneficial attributes such as metal-chelating, antioxidant, anti-glycation, and anti-crosslinking [128,129]. In particular, carnosine is used for the treatment of cataracts owing to its anti-crosslinking ability [130]. The protective activity of carnosine against the accumulation of AβP has also been reported [50].…”

Section: Discussionmentioning

confidence: 99%

Implications of Metal Binding and Asparagine Deamidation for Amyloid Formation

Sadakane

Kawahara

2018

IJMS

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Increasing evidence suggests that amyloid formation, i.e., self-assembly of proteins and the resulting conformational changes, is linked with the pathogenesis of various neurodegenerative disorders such as Alzheimer’s disease, prion diseases, and Lewy body diseases. Among the factors that accelerate or inhibit oligomerization, we focus here on two non-genetic and common characteristics of many amyloidogenic proteins: metal binding and asparagine deamidation. Both reflect the aging process and occur in most amyloidogenic proteins. All of the amyloidogenic proteins, such as Alzheimer’s β-amyloid protein, prion protein, and α-synuclein, are metal-binding proteins and are involved in the regulation of metal homeostasis. It is widely accepted that these proteins are susceptible to non-enzymatic posttranslational modifications, and many asparagine residues of these proteins are deamidated. Moreover, these two factors can combine because asparagine residues can bind metals. We review the current understanding of these two common properties and their implications in the pathogenesis of these neurodegenerative diseases.

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“…Animal studies indicate that carnosine is beneficial towards senescence-accelerated mice [131] and may have therapeutic potential where deleterious aldehydes such as MG appear to be important in age-related pathologies [132] such as diabetes [127,133,134], diabetic kidney disease [134-136], atherosclerosis [137-139] and cataractogenesis [140-144] as well as models of stroke [145-148], Alzheimer’s disease [149-151] and PD [152-154]. …”

Section: Endogenous Control Of Mg-mediated Damagementioning

confidence: 99%

On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson’s Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine

Hipkiss¹

2017

Aging and disease

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Recent research shows that energy metabolism can strongly influence proteostasis and thereby affect onset of aging and related disease such as Parkinson’s disease (PD). Changes in glycolytic and proteolytic activities (influenced by diet and development) are suggested to synergistically create a self-reinforcing deleterious cycle via enhanced formation of triose phosphates (dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate) and their decomposition product methylglyoxal (MG). It is proposed that triose phosphates and/or MG contribute to the development of PD and its attendant pathophysiological symptoms. MG can induce many of the macromolecular modifications (e.g. protein glycation) which characterise the aged-phenotype. MG can also react with dopamine to generate a salsolinol-like product, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinaline (ADTIQ), which accumulates in the Parkinson’s disease (PD) brain and whose effects on mitochondria, analogous to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), closely resemble changes associated with PD. MG can directly damage the intracellular proteolytic apparatus and modify proteins into non-degradable (cross-linked) forms. It is suggested that increased endogenous MG formation may result from either, or both, enhanced glycolytic activity and decreased proteolytic activity and contribute to the macromolecular changes associated with PD. Carnosine, a naturally-occurring dipeptide, may ameliorate MG-induced effects due, in part, to its carbonyl-scavenging activity. The possibility that ingestion of highly glycated proteins could also contribute to age-related brain dysfunction is briefly discussed.

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Analytical and physicochemical characterisation of the senile cataract drug dipeptide β-alanyl-L-histidine (carnosine)

Cited by 20 publications

References 16 publications

On the Anticataractogenic Effects of L‐Carnosine: Is It Best Described as an Antioxidant, Metal‐Chelating Agent or Glycation Inhibitor?

On the Anticataractogenic Effects of L‐Carnosine: Is It Best Described as an Antioxidant, Metal‐Chelating Agent or Glycation Inhibitor?

Implications of Metal Binding and Asparagine Deamidation for Amyloid Formation

On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson’s Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine

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