• 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.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.

• Nutrition Research and Practice
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• v.14 no.3
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• pp.188-202
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• 2020

BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging. MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS: To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

• 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.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.271-279
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• 2022

Background: Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Methods: Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. Results: The results showed that the co-administration of acetaminophen and L-carnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group. There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. Conclusions: Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCI-induced peripheral neuropathy in Wistar rat.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.50 no.5
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• pp.520-526
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• 2017

Carnosine was recently reported to protect against the DNA damage induced by oxidative stress. In this study, we investigated the protective effect of eel Anguilla japonica carnosine extracts prepared using different methods (heat treatment extracts, HTEs; ion exchange chromatography, IEC; ultrafiltration permeation, UFP) on leukocyte DNA damage using the comet assay. Human leukocytes were incubated with extracts of eel carnosine at concentrations (of 10, 50, $100{\mu}g/mL$), and then subjected to an oxidative stimulus [$200{\mu}M$ hydrogen peroxide ($H_2O_2$)]. Pretreatment of the cells for 30 min with carnosine significantly reduced the genotoxicity of $H_2O_2$ measured as DNA strand breaks. The protective effects of the three types of extract (HTE, IEC, and UFP) increased with concentration. At the highest concentration (100 g/mL). there were no statistical differences in oxidative damage between each extract treatment and PBS-treated negative controls. When leukocytes were incubated with carnosine for 30 min after exposure to $H_2O_2$. the protective ability of each extract changed. Therefore, eel carnosine inhibits the $H_2O_2$ induced damage to cellular DNA in human leukocytes, supporting the protective effect of this compound against oxidative damage.

• Korean Journal of Veterinary Research
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• v.50 no.2
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• pp.105-111
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• 2010

Carnosine is a dipeptide $(\beta-alanyl-L-histidine)$ found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels, glucose tolerance test (GTT), glycosylated hemoglobin, and serum biochemical and lipid levels in streptozotocin-induced diabetic mice. There were five experimental groups including normal (ICR mice), control (saline), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w.. Carnosine was orally administered to the diabetic mice everyday for 12 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine at the dose of 6 mg/kg significantly decreased the blood glucose level compared with the control at 2 and 4 weeks. The treatments of carnosine at the doses of 6 and 30 mg/kg significantly decreased the blood glucose levels in GTT and glycosylated hemoglobin compared with the control. Carnosine significantly increased total proteins compared with the control. Carnosine at the dose of 6 mg/kg significantly decreased total cholesterol and triglyceride in the serum compared to the control. These results suggest that carnosine at a low level has a hypoglycermic effect resulting from reduction of blood glucose and that a carnosine-containing diet or drug may give a benefit for controlling diabetes mellitus in humans.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.731-734
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• 2012

• BMB Reports
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• v.45 no.2
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• pp.114-119
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• 2012

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegeneration. Oxidative modification of neurofilament proteins has been implicated in the pathogenesis of neurodegenerative disorders. In this study, oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory effects of histidyl dipeptides on NF-L modification were investigated. When NF-L was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in a time-dependent manner. We also found that the generation of hydroxyl radicals (${\bullet}OH$) was linear with respect to the concentrations of salsolinol as a function of incubation time. NF-L exposure to salsolinol produced losses of glutamate, lysine and proline residues. These results suggest that the aggregation of NF-L by salsolinol may be due to oxidative damage resulting from free radicals. Carnosine, histidyl dipeptide, is involved in many cellular defense processes, including free radical detoxification. Carnosine, and anserine were shown to significantly prevent salsolinol-mediated NF-L aggregation. Both compounds also inhibited the generation of ${\bullet}OH$ induced by salsolinol. The results indicated that carnosine and related compounds may prevent salsolinol-mediated NF-L modification via free radical scavenging.

• 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.