• Bulletin of the Korean Chemical Society
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• v.26 no.8
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• pp.1251-1254
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• 2005

It has been proposed that oxidation of L-3,4-dihydroxyphenylalanine (DOPA) may contribute to the pathogenesis of neurodegenerative disease. In this study, L-DOPA-Fe(III)-mediated DNA cleavage and the protection by carnosine and homocarnosine against this reaction were investigated. When plasmid DNA was incubated with L-DOPA in the presence of Fe(III), DNA strand was cleaved. Radical scavengers and catalase significantly inhibited the DNA breakage. These results suggest that $H_2O_2$ may be generated from the oxidation of DOPA and then $Fe^{3+}$ likely participates in a Fenton’s type reaction to produce hydroxyl radicals, which may cause DNA cleavage. Carnosine and homocarnosine have been proposed to act as anti-oxidants in vivo. The protective effects of carnosine and homocarnosine against L-DOPA-Fe(III)-mediated DNA cleavage have been studied. Carnosine and homocarnosine significantly inhibited DNA cleavage. These compounds also inhibited the production of hydroxyl radicals in L-DOPA/$Fe^{3+}$ system. The results suggest that carnosine and homocarnosine act as hydroxyl radical scavenger to protect DNA cleavage. It is proposed that carnosine and homocarnosine might be explored as potential therapeutic agents for pathologies that involve damage of DNA by oxidation of DOPA.

• Bulletin of the Korean Chemical Society
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• v.27 no.5
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• pp.663-666
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• 2006

Carnosine, homocarnosine and anserine might act as anti-oxidants and free radical scavengers in vivo. In the present study, the protective effects of carnosine and related compounds on the $H_2O_2$-mediated cytochrome c modification were studied. Carnosine, homocarnosine and anserine significantly inhibited the oligomerization of cytchrome c induced by $H_2O_2$. All three compounds also inhibited the formation of carbonyl compound and dityrosine during the incubation of cytochrome c with $H_2O_2$. These compounds effectively inhibited the peroxidase activity in the cytchrome c treated with $H_2O_2$. The results suggested that carnosine, homocarnosine, and anserine might protect cytochrome c against $H_2O_2$-mediated oxidative damage through a free radical scavenging.

• BMB Reports
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• v.43 no.10
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• pp.683-687
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• 2010

Previous studies have shown that one of the primary causes of increased iron content in the brain may be the release of excess iron from intracellular iron storage molecules such as ferritin. Free iron generates ROS that cause oxidative cell damage. Carnosine and related compounds such as endogenous histidine dipetides have antioxidant activities. We have investigated the protective effects of carnosine and homocarnosine against oxidative damage of DNA induced by reaction of ferritin with $H_2O_2$. The results show that carnosine and homocarnosine prevented ferritin/$H_2O_2$-mediated DNA strand breakage. These compounds effectively inhibited ferritin/$H_2O_2$-mediated hydroxyl radical generation and decreased the mutagenicity of DNA induced by the ferritin/$H_2O_2$ reaction. Our results suggest that carnosine and related compounds might have antioxidant effects on DNA under pathophysiological conditions leading to degenerative damage such as neurodegenerative disorders.

• BMB Reports
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• v.32 no.4
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• pp.350-357
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• 1999

At concentrations of 1 mM, the protective effects of carnosine and related compounds including anserine, homocarnosine, histidine, ${\beta}$-alanine were investigated against copper-catalyzed oxidative damage to deoxyribose, ascorbic acid, human serum albumin, liposome, and erythrocytes. Carnosine and anserine reduced Cu (II) to bathocuproine-reactive Cu (I) in a time- a and a dose-dependent manner while the others did not. Carnosine reduced 86% of $100\;{\mu}M$ Cu (II) in 60 min. Carnosine, homocarnosine, anserine, and histidine inhibited copper-catalyzed deoxyribose degradation by 75, 66, 65, and 45%, respectively. In the presence of $1\;{\mu}M$ Cu (II), carnosine and related compounds inhibited ascorbic acid oxidation by 55-85% after incubation for 20 min. In the presence of 0.15 mM ascorbic acid and 0.8 mM $H_2O_2$, carnosine, anserine, homocarnosine, and histidine inhibited copper-catalyzed oxidation of human serum albumin by 41, 21, 29, and 24%, respectively, as determined by carbonyl formation. These compounds also significantly inhibited copper-catalyzed liposomal lipid peroxidation as measured by malondialehyde and lipid hydroperoxides. Carnosine, anserine, homocarnosine, and histidine inhibited hemolysis of bovine erythrocytes induced by 0.1 mM Cu (II). These results suggest that histidine-containing dipeptides may play an important role in protecting against free radical-mediated tissue damage.

• Bulletin of the Korean Chemical Society
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• v.27 no.6
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• pp.830-834
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• 2006

Lipid peroxidation induced by the reaction of cytochrome c with $H_2O_2$ was investigated. When linoleic acid micelles or phosphatidyl choline liposomes were incubated with cytochrome c and $H_2O_2$, lipid peroxidation was increased in cytochrome c and $H_2O_2$ concentrations-dependent manner. Radical scavengers, azide, formate and ethanol prevented lipid peroxidation induced by the cytochrome c/$H_2O_2$ system. Iron specific chelator, desferoxamine also prevented the cytochrome c/$H_2O_2$ system-mediated lipid peroxidation. These results suggest that lipid peroxidation may be induced by the cytochrome c/$H_2O_2$ system via the generation of free radicals. Carnosine, homocarnosine and anserine are present in the muscle and brain of many animals and human. Previous studies show that these compounds have an antioxidant function. In the present study, carnosine, homocarnosine and anserine significantly prevented the cytochrome c/$H_2O_2$ system-mediated lipid peroxidation. Carnosine and related compounds also inhibited the free radical-generating activity of cytochrome c. The results suggest that carnosine, homocarnosine and anserine may prevent lipid peroxidation induced by the cytochrome c/$H_2O_2$ system through a free radical scavenging.

• Bulletin of the Korean Chemical Society
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• v.27 no.11
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• pp.1891-1893
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• 2006

• Bulletin of the Korean Chemical Society
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• v.29 no.9
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• pp.1732-1736
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• 2008

The endogenous dipeptides, carnosine and related compounds, are the naturally occurring dipeptides with multiple neuroprotective properties. We have examined the protective effects of carnosine, homocarnosine and anserine on the aggregation of neurofilament-L (NF-L) induced by neurotoxin, acrolein. When NF-L was incubated with acrolein in the presence of carnosine, homocarnosine or anserine, protein aggregation was inhibited in a concentration-dependent manner. These compounds inhibited the formation of protein carbonyl compounds and dityrosine in acrolein-mediated NF-L aggregates. The aggregates of NF-L displayed thioflavin T reactivity, reminiscent of amyloid. This thioflavin T reactivity was inhibited by carnosine and related compounds. This effect was associated with decreased formation of oxidatively modified proteins. Our results suggested that carnosine and related compounds might have protective effects to brain proteins under pathophysiological conditions leading to degenerative damage such as neurodegenerative disorders.

• BMB Reports
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• v.40 no.1
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• pp.125-129
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• 2007

Neurofilament-L (NF-L) is a major element of the neuronal cytoskeleton and is essential for neuronal survival. Moreover, abnormalities in NF-L result in neurodegenerative disorders. Carnosine and the related endogeneous histidine dipeptides prevent protein modifications such as oxidation and glycation. In the present study, we investigated whether histidine dipeptides, carnosine, homocarnosine, or anserine protect NF-L against oxidative modification during reaction between cytochrome c and $H_2O_2$. Carnosine, homocarnosine and anserine all prevented cytochrome c/$H_2O_2$-mediated NF-L aggregation. In addition, these compounds also effectively inhibited the formation of dityrosine, and this inhibition was found to be associated with the reduced formations of oxidatively modified proteins. Our results suggest that carnosine and histidine dipeptides have antioxidant effects on brain proteins under pathophysiological conditions leading to degenerative damage, such as, those caused by neurodegenerative disorders.

• Toxicological Research
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• v.15 no.1
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• pp.109-115
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• 1999

The antiosidant activity of carnosine and related compounds such as anserine, homo-carnosine, histidine, and $\beta$-alanine which are found in most mammalian tissues, was investigated using hypochlorite (HOCl)-induced oxidant systems. Carnosine and related compounds were protective against HOCl-induced ascorbic acid oxidation, as determined by UV absorbance at 265nm. L-histidine was the most effective among them. The inhibitory effect of these compounds was strongly associated with a decrease in HOCl. It was also found that carnosine and related compounds significantly protected against the HOCl-mediated erythrocyte damage, as determined by hemoglobin release and gemolysis (p<0.05). Carnosine and anserine also inhibited of $\alpha$-antiprotease($\alpha$-AP) by HOCl, thereby inactivating porcine elastase. The inhibitory effect of carnosine on inactivation of $\alpha$-AP by HOCl depended on the concentration of carnosine and on the time preincubated with HOCl. Homocarnosine, histidine, and $\beta$-alanine did not inhibit the reaction. These results indicate that carnosine and related compounds can neutralize or scavenge HOCl. Thus, these compounds may play an important role in protecting against HOCl-mediated damage of biomolecules in vivo.

• BMB Reports
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• v.32 no.4
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• pp.370-378
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• 1999

The effects of carnosine and related compounds (CRC) including anserine, homocarnosine, histidine, and ${\beta}$-alanine, found in most mammalian tissues, were investigated on in vitro glucose oxidation and glycation of human serum albumin (HSA). Carnosin and anserine were more reactive with D-glucose than with L-lysine. In the presence of $10\;{\mu}M$ Cu (II), although carnosine and anserine at low concentrations effectively inhibited formation of ${\alpha}$-ketoaldehyde from D-glucose, they increased generation of $H_2O_2$ in a dose-dependent manner. Carnosine, homocarnosine, anserine, and histidine effectively inhibited hydroxylation of salicylate and deoxyribose degradation in the presence of glucose and $10\;{\mu}M$ Cu (II). In the presence of 25 mM D-glucose, copper and ascorbic acid stimulated carbonyl formation from HSA. Except for ${\beta}$-alanine, CRC effectively inhibited the copper-catalyzed carbonyl formation from HSA. The addition of 25 mM D-glucose and/or $10\;{\mu}M$ Cu (II) to low density lipoprotein (LDL) increased formation of conjugated dienes. CRC effectively inhibited the glucose and/or copper-catalyzed LDL oxidation. CRC also inhibited glycation of HSA as determined by hydroxymethyl furfural and lysine with free ${\varepsilon}$-amino group. These results suggest that CRC may play an important role in protecting against diabetic complications by reacting with sugars, chelating copper, and scavenging free radicals.