A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma / 中华肝脏病杂志

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Mitochondrial energy metabolism in baby hamster kidney (BHK-21/C13) cells treated with karnozin extra® / Metabolismo energético mitocondrial en células de riñón de hámster bebé (BHK-21 / C13) tratadas con karnozin extra®

SUMMARY: Carnosine is known as a natural dipeptide, which inhibits the proliferation of tumor cells throughout its action on mitochondrial respiration and cell glycolysis. However, not much is known about its effects on the metabolism of healthy cells. We explored the effects of Karnozin EXTRA® capsule with different concentrations of L-carnosine, on the cell viability and the expressions of intermediate filament vimentin (VIM) and superoxide dismutase (SOD2) in normal fibroblasts BHK-21/C13. Furthermore, we investigated its action on the energy production of these cells. Cell viability was quantified by the MTT assay. The Clark oxygen electrode (Oxygraph, Hansatech Instruments, England) was used to measure the "intact cell respiration rate", state 3 of ADP-stimulated oxidation, maximum oxidation capacity and the activities of complexes I, II and IV. Results showed that Karnozin EXTRA® capsule in concentrations of 2 and 5 mM of L-carnosine did not induce toxic effects and morphological changes in treated cells. Our data revealed a dose-dependent immunofluorescent signal amplification of VIM and SOD2 in the BHK-21/C13 cell line. This supplement substantially increased the recorded mitochondrial respiration rates in the examined cell line. Due to the stimulation of mitochondrial energy production in normal fibroblasts, our results suggested that Karnozin EXTRA® is a potentially protective dietary supplement in the prevention of diseases with altered mitochondrial function.

RESUMEN: La carnosina se conoce como dipéptido natural, que inhibe la proliferación de células tumorales a través de su acción sobre la respiración mitocondrial y la glucólisis celular. Sin embargo, no se sabe mucho de sus efectos sobre el metabolismo de las células sanas. Exploramos los efectos de la cápsula Karnozin EXTRA® con diferentes concentraciones de L-carnosina, sobre la viabilidad celular y las expresiones de vimentina de filamento intermedio (VIM) y superóxido dismutasa (SOD2) en fibroblastos normales BHK-21 / C13. Además, estudiamos su acción sobre la producción de energía de estas células. La viabilidad celular se cuantificó mediante el ensayo MTT. Se utilizó el electrodo de oxígeno Clark (Oxygraph, Hansatech Instruments, Inglaterra) para medir la "tasa de respiración de células intactas", el estado 3 de oxidación estimulada por ADP, la capacidad máxima de oxidación y las actividades de los complejos I, II y IV. Los resultados mostraron que la cápsula de Karnozin EXTRA® en concentraciones de 2 y 5 mM de L- carnosina no indujo efectos tóxicos ni cambios morfológicos en las células tratadas. Nuestros datos revelaron una amplificación de señal inmunofluorescente dependiente de la dosis de VIM y SOD2 en la línea celular BHK-21 / C13. Este suplemento aumentó sustancialmente las tasas de respiración mitocondrial registradas en la línea celular examinada. Debido a la estimulación de la producción de energía mitocondrial en fibroblastos normales, nuestros resultados sugirieron que Karnozin EXTRA® es un suplemento dietético potencialmente protector en la prevención de enfermedades con función mitocondrial alterada.

A method for examination of L-carnosine， eyeseryl，glutathione and acetyl hexapeptide-8 in cosmetics by HPLC / 上海预防医学

［ Objective:To establish a HPLC method for examination of L-carnosine，eyeseryl，glutathione and acetyl hexapeptide-8 in cosmetics. Method:After being extracted by water， L-carnosine， Eyeseryl， Glutathione， and Acetyl Hexapeptide-8 were examined by HPLC with methanol-0.01% formic acid （V/V） aqueous solution as the mobile phase. The column was Agilent Eclipse XDB-C18 （5 μm， 4.6 mm×150 mm）. The flow rate was 0.5 mL/min. The determination wavelength was set at 210 nm. Results:There was a good linear relationship within the range of 5-100 μg/mL for L-carnosine， eyeseryl， glutathione， and acetyl hexapeptide-8. The recoveries of L-carnosine Eyeseryl Glutathione and Acetyl Hexapeptide-8 were between 92.5%~105.9%， with a RSD from 0.5% to 3.5%. Conclusion:The method is simple， sensitive， specific and reproducible in the examination of L-carnosine， Eyeseryl， Glutathione， and Acetyl Hexapeptide-8 in cosmetics.

Clinical analysis of hormone combined with cerebral glycoside carnosine and dehydrating drugs in the treatment of traumatic optic nerve injury / 中华急诊医学杂志

Objective:To retrospectively analyze the effect of hormone combined with cerebral glycoside carnosine and dehydration drugs in traumatic optic neuropathy (TON) patients.Methods:The enrolled 215 TON patients in our hospital from February 2014 to September 2021 were randomly divided into the combination group ( n=143) and routine group ( n=142). The baseline data, visual acuity recovery before and after treatment and adverse reactions of each group were compared. Univariate analysis was conducted to analyze the differences in indicators of good prognosis and visual acuity improvement between the two groups. Results:The effective rate of vision recovery in the combination group was significantly increased than that in the routine group ( P<0.05). After treatment, the intraocular pressure and visual field defect in the combination group were significantly decreased than those in the routine group ( P<0.05). Univariate subgroup analysis showed that there were statistically significant differences between TON patients with age ≤40 years, residual light sensation after injury, visit time ≤24 h, and VEP not extinguished with combined treatment of hormone, brain glycoside carnotin and dehydrating drugs and the routine group ( P<0.05). Univariate subgroup analysis showed that TON patients with optic canal fracture without optic nerve swelling and tortuosity had a good prognosis after treatment with combined hormone, cerebral glucoside carnosine and dehydration, which was statistically different from that in the routine group ( P<0.05). Conclusions:Brain glycosides carnosine and dehydration therapy on the basis of combined hormone a prednisolone sodium succinate treatment can improve vision in TON patients, lighten the optic nerve injury, will not increase the occurrence risk of adverse reactions, and have higher security. It is necessary to focus on high-risk patient over 40 years old, more than 24 h of treatment time, VEP extinction, optic nerve swelling poor efficacy. It is worthy of clinical promotion.

Effect Of Ophiocephalus Striatus Extract On Carnosine Dipeptidase-1 Plasma Level In Cancer Cachexia Patients

The objective of this study is to find the association between Ophiocephalus striatus extract supplementation and carnosine dipeptidase-1 plasma level in patient with cancer cachexia. This study was an open label study in which all subject knew the purpose of this study and understood the intervention they will get. The design for this study was one group pretest and posttest with inclusion and exclusion criteria to choose the ideal subject for this study. Descriptive statistics analysis used for demographic data and Wilcoxon test used to test numeric variable in study ®treatment groups before and after treatment. Subjects were treated with vipAlbuminsupplementation which contains 5000 mg Ophiocephalus striatus extract in 2 weeks period. The result from this study shows raised in Carnosine Dipeptidase-1 plasma level before and after treatment with Ophiocephalus striatus extract (p=0.007).

The protective effect of l-carnosine on neurotoxicity of deguelin-induced SH-SY5Y cells / 中国药理学通报

Aim: To study the protective effect of L-carnosine on deguelin-induced neurotoxicity. Methods: SH-SY5Y cells were treated with 1, 10, 20, 40, 60, 80, 100 mmol · L" L-carnosine for 24 h; cell viability was detected by CCK-8 assay. SH-SY5Y cells were respectively treated with 30 mmol · L-1 L-carnosine, 20 μmol · L-1 deguelin, 20 μmol · L-1 deguelin with 30 mmol · L-1 L-carnosine for 24 h; AO/EB method was employed for observing the morphology and apoptotic morphology of treated cells. SH-SY5Y cells were respectively treated with 8 μmol · L-1 deguelin, 8 μmol · L-1 deguelin with 3 mmol · L-1 L-carnosine, 8 μmol · L-1 deguelin with 30 mmol · L-1 L-carnosine, 30 mmol · L-1 L-carnosine, 20 μmol · L-1 deguelin, 20 μmol · L-1 deguelin with 3 mmol · L-1 L-carnosine, 20 μmol · L-1 deguelin with 30 mmol · L-1 L-carnosine, 50 μmol · L-1 deguelin, 50 μmol · L-1 deguelin with 3 mmol · L-1 L-carnosine, 50 μmol · L-1 deguelin with 30 mmol · L-1 L-carnosine for 24 h. Cell proliferation was detected by CCK-8 assay; apoptotic rate of treated cells was determined by flow cytometry; the reactive oxygen species (ROS) of treated cells was detected by DCFH-DA staining flow cytometry. Results: After 30 mmol · L-1 L-carnosine was co-treated with 20 μmol · L-1 and 50 μmol · L-1 of deguelin, the cell inhibitory rate decreased by 9. 07% and 6. 1%, the number of early apoptotic cells decreased, and the early apoptotic rate decreased by 9. 35%. The total apoptotic rate decreased by 10. 7%, and the ROS level was lower than that of the deguelin alone treatment group. The difference was statistically significant (P < 0. 05). Conclusions: L-carnosine can effectively reduce the neurotoxicity of deguelin-induced SH-SY5Y cells, which may be related to the reduction of oxidative stress levels, thereby inhibiting apoptosis and protecting cells.

Investigação dos processos biológicos associados à produção endógena de aldeídos reativos / Research on biological processes associated with endogenous production of reactive aldehydes

Os aldeídos são espécies reativas que podem ser produzidos endogenamente por processos como a lipoperoxidação, podendo reagir com lipídios, proteínas e DNA. Diversas evidências apontam para o envolvimento de aldeídos reativos na progressão de patologias como doenças cardiovasculares, arteriosclerose e doenças neurodegenerativas. Uma meta central do CEPIDRedoxoma é estudar a reatividade química de intermediários redox em ambientes biológicos e consequentes mudanças na estrutura e função de biomoléculas, entender como cada intermediário redox reage com biomoléculas específicas e os efeitos resultantes, essenciais para a concepção de biomarcadores e antioxidantes. O nosso grupo estuda os mecanismos de formação, detoxificação e reação com biomoléculas de aldeídos reativos endógenos e exógenos e seu papel em patologias como a esclerose lateral amiotrófica (ALS). Um dos mecanismos de detoxificação desses aldeídos é através da conjugação com a carnosina. Recentemente, foi observado que a suplementação de animais transgênicos ALS SOD G93A com carnosina via oral resultou em retardo da perda de peso e tendência de aumento da sobrevida dos animais. O presente projeto buscou investigar o possível papel da carnosina em animais modelo para ALS. Para isso as modificações em DNA induzidas por aldeídos reativos e a formação de adutos de carnosina-aldeídos foram analisadas através de metodologia HPLC-MS/MS. Assim observamos que ratos suplementados com carnosina apresentaram níveis significativamente menores de proteína carbonilada em músculo e fígado. Em fígadoforam vistos níveis menores de dois adutos de DNA, 8-oxodGuo e1,N2-HO-propanodGuo, em animais suplementados. Em cérebro foram detectados níveis menores de 1, N2-εdGuo. Com relação aos adutos carnosina-aldeídos, foi observado níveis significativamente maiores do aduto CAR-HHE na medula. Com embasamento nos resultados aqui apresentados, sugere-se a utilização de sequestradores de aldeídos como uma estratégia terapêutica em condições fisiopatológicas nas quais ao acúmulo dessas espécies está comprovado

Aldehydes are reactive species that can be produced endogenously by processes such as lipid peroxidation, which can react with lipids, proteins and DNA. Several evidences point to the involvement of reactive aldehydes in the progression of pathologies such as cardiovascular diseases, atherosclerosis and neurodegenerative diseases. A central goal of CEPID-Redoxoma is to study the chemical reactivity of redox intermediates in biological environments and consequent changes in the structure and function of biomolecules, to understand how each redox intermediate reacts with specific biomolecules and the resulting effects, essential for the design of biomarkers and antioxidants. Our group studies the mechanisms of formation, detoxification and reaction with biomolecules of endogenous and exogenous reactive aldehydes and their role in pathologies such as amyotrophic lateral sclerosis (ALS). One of the detoxification mechanisms of these aldehydes is through carnosine conjugation. Recently, we observed that oral carnosine supplementation in transgenic ALS SODG93A animals resulted in delayed weight loss and a tendency to increase the survival of the animals. The present project investigated the potential role of carnosine in animal models for ALS. Thus, reactive aldehydes induced DNA modifications and carnosine aldehyde adducts were analyzed by HPLC-MS/MS. We observed that rats supplemented with carnosine presented significantly lower levels of protein carbonylation in muscle and liver. Lower levels of two DNA adducts, 8-oxodGuo and 1, N2-HO-propanodGuo, were observed in liver of the supplemented animals. Lower levels of 1, N2-εdGuo were detected in the brain. Regarding the carnosine-aldehydeadducts, significantly higher levels of the CAR-HHE adduct were observed in spinal cord. The results presented here suggest the use of aldehyde scavengers as a therapeutic strategy under pathological conditions in which is proven the accumulation of these species

The role of carnosine on the oxidation reaction in vitro / 安徽医科大学学报

In this study, HRP or FeCl3were used as the catalysts in MTT, TMB and Mino reaction system, the effects of carnosine on the oxidation reaction were evaluated respectively. Indeed, carnosine was a pro-oxidant in luminol reaction, however an anti-oxidant in MTT assay. Once TMB was its substrate, carnosine was neutral in oxi-dation. Thus, it is supposed that the oxidative property of carnosine depends on the substrates.

Study in L-carnosine on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells / 局解手术学杂志

Objective To study the L-carnosine induced apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism.Methods Human hepatocellular carcinoma HepG2 cells were cultured in vitro,then the cells in logarithmic phase were divided into 5 mM,20 mM,50 mM L-carnosine group and control group,treated with 5 mM,20 mM,50 mM L-carnosine and saline respectively.The proliferation of HepG2 cells was measured by CCK-8 assay after 24 hours and 48 hours treatment.The cell apoptosis and cell cycle were detected by flow cytometry after 48 hours treatment.The protein expression of Caspase-8,PI3K and Akt were detected by Western blot in each group after 48 hours treatment.Results CCK-8 and flow cytometry assay showed that both 20 mM and 50 mM L-carnosine treated group significantly inhibited the proliferation of HepG2 cells after 24 hours and 48 hours,and the inhibition were in a time and dose-dependent manner.Western blot revealed that the expressions of PI3K and Akt were down-regulated with the increase of L-carnosine concentration,while the expression of Caspase-8 was increased.Conclusion L-carnosine exhibits an inhibitory effect of the proliferation and promote apoptosis of human liver cancer cell line HepG2.The mechanism may be associated with the inhibition of the PI3K/Akt signaling pathway and activation of Caspase-8 signaling pathway.

Regulating Effect Of Carnosine And /Or L- Arginine On The Expression Of Inflammatory Molecules Induced Nephropathy In The Hypoxic Rat Model

This study aimed to explore the effective role of carnosine and /or L- arginine in down regulation of the inflammatory molecule expression caused renal damage in response to sodium nitrite (NaNO2) induced hypoxia in rats . NaNO2 was administered subcutaneously (s.c.) to rats as a single dose (60 mg/kg body weight ). L-arginine (200mg/Kg body weight) and carnosine (250 mg/ Kg body weight ) were administered (i.p.) as a single dose , 24 h before NaNO2 injection. The results revealed that pre- administration of arginine and /or carnosine to NaNO2 hypoxic rats, significantly modulated the increases in serum markers of renal function (creatinine and urea) as well as the decrease in hemoglobin (Hb) level versus hypoxic rats. The two agents each alone or in a combination, markedly down regulated the serum pro-inflammatory molecules, including tumor necrosis factor-α (TNF- α) , C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and heat shock protein -70 (HSP-70) as well as interleukin-6 (IL-6) in renal tissue compared to NaNO2 hypoxic rats . Also, the two agents successfully down modulated the alteration in the serum hypoxia inducible factor 1α (HIF 1α) . The present biochemical results were also supported by histopathological examination. In conclusion, the current data revealed that although the efficacy of arginine or carnosine each alone, their combination was more effective in ameliorating the renal damage induced by inflammatory molecules in response to NaNO2 hypoxia . This may support the use of this combination as an effective drug to treat hypoxic renal damage

Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2) and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs.

Protective effect of carnosine on Glutamate induced apoptosis in SH-SY5 Y cells / 中国生化药物杂志

Objective To investigate the protective effect of carnosine on Glutamate induced apoptosis in SH-SY5Y cells and its mechanism. Methods The injury model was established by treating SH-SY5Y cells with glutamate in vitro.Inverted microscope was used to observe cell morphology. The cell viability was detected by MTT assay, and changes in nucleus were detected by Hoechst33258 staining under fluorescence microscopy.The cell apoptosis rates were measured by flow cytometry.The reactive oxygen species ( ROS ) level in cells was detected by fluorescent probe CDFH-DA. Results Compared with normal control group, the cell viability in glutamate group decreased (P<0.01), the morphology changes of cell apoptosis such as karyopyknosis and split were observed by Hoechst33258 staining, while the apoptosis rate and the level of ROS were increased (P<0.01). Compared with glutamate group, the cell viability of carnosine 0.6,3,15 mmol/L groups obviously increased(P<0.01), while the morphology changes of cell apoptosis significantly improved, the apoptosis rate and the level of ROS were obviously reduced ( P<0.01 ) .Compared with normal control group, the cell viability, the morphology changes and the apoptosis rate did not significantly change in carnosine group.The level of ROS was reduced, but there was no statistically significant difference between two groups.Conclusion Carnosine has apparent protective effect on apoptosis of SH-SY5Y cells injury induced by glutamate.The mechanism may be related to carnosine prevent the occurrence of oxidative stress.

Neuroprotective of carnosine on oxygen-glucose deprivation/reperfusion induced injury in rat brain slices / 中国生化药物杂志

Objective To investigate effect of carnosine on oxygen glucose deprivation/reperfusion ( OGD/RP) induced injury in rat brain slices. Methods Injury of brain slices was determined by TTC methods.The contents of ATP, ADP and AMP were determined by high performance liquid chromatography.Reactive Oxygen species ( ROS) were determined by fluorescence methods.Results Compared with control group, rat hippocampal slices were significantly damaged by OGD/RP, indicated by light color and decreased A490 nm value of TTC staining.Meanwhile the contents of ATP and ADP were significantly decreased, and the content of AMP and ROS were significantly increased, the difference between two group was significant ( P<0.01).Pre-incubation with Carnosine (1000, 200, 40 μg/mL) significantly inhibited the light color and decreased A490 nm value of TTC staining, increased the contents of ATP, ADP and AMP, and decreased the content of ROS, the difference between two group was significant ( P <0.01 ) . Conclusion Carnosine can protect rat hippocampal slices against injury induced by OGD/RP, which may relate to improve the energy metabolism and strengthen the ability of anti-oxidative stress.

The influence of carnosine in expression levels of bcl-2 and bax after focal cerebral ischemia in rats / 天津医药

Objective To explore the effect of carnosine in the expression of B cell lymphomal/leukemia-2 (bcl-2) and bcl-2-associated X protein (bax) after focal cerebral ischemia in rats. Methods Thirty male SD rats (SPF scale) were ran?domly divided into 3 groups:sham-operated group, model group and carnosine treated group (n=10 for each group). The mid?dle cerebral artery occlusion model (MCAO) was induced in model group and carnosine treated group. Rats were received carnosine [1 000 mg/(kg·d), orally] in carnosine treated group, and the other rats were received the same volume of normal sa?line (NS) in shame-operated group and model group. The neurological deficit score was used to evaluate the neurological function at 24 h and 72 h after MCAO. Morphological changes were observed by HE staining. TCC staining was used to label infarct volume, and immunohistochemistry was used to detect the expression of bcl-2 and bax. Results Compared with model group, the score of neurological function and infarct volume were significantly declined in carnosine treated group at 72 h after injury (P<0.05 or P<0.01). The changes of ischemic impairment were lighter in carnosine treated group than that of model group. Compared with sham-operated group, the expression levels of bcl-2 and the ratio of bcl-2/bax were de?creased while the expression of bax was increased in model group (P<0.05). Compared with model group, carnosine could sig?nificantly increase the expression of bcl-2 and the ratio of bcl-2/bax, and reduce the expression of bax (P<0.01 or P<0.05). Conclusion Carnosine can enhance bcl-2 expression, decrease bax expression and increase the ratio of bcl-2/bax, which is likely to be one of the mechanisms of neuroprotection.

Effect of ß-alanine supplementation on 20 km cycling time trial performance

The effects of ß-alanine supplementation on high-intensity cycling performance and capacity have been evaluated, although the effects on longer duration cycling performance are unclear. Nineteen UK category 1 male cyclists completed four 20 km cycling time trials, two before and two after supplementation with either 6.4 g•d-1 ß-alanine (n = 10; BA) or a matched placebo (n = 9; P). Performance time for the 20 km time trial and 1 km split times were recorded. There was no significant effect of ß-alanine supplementation on 20 km time trial performance (BA-pre 1943 ± 129 s; BA-post 1950 ± 147 s; P-pre 1989 ± 106 s; P-post 1986 ± 115 s) or on the performance of each 1 km split. The effect of ß-alanine on 20 km time trial performance was deemed unclear as determined by magnitude based inferences. Supplementation with 6.4 g•d-1 of ß-alanine for 4 weeks did not affect 20 km cycling time trial performance in well trained male cyclists

Protective effect of carnosine on cognitive impairment induced by subcortical ischemic vascular dementia / 中国药理学通报

Aim Subcortical ischemic vascular demen-tia ( SIVD ) induced by chronic hypoperfusion due to small-artery disease is a common cause of vascular de-mentia ( VaD) , which is recognized as the second most prevalent type of dementia. The aim of this study was to determine whether carnosine played a protective role in cognitive impairment induced by permanent occlu-sion of the right unilateral common carotid arteries ( rUCCAO ) in SIVD. Methods Adult male mice ( C57BL/6 strain ) were subjected to rUCCAO, and treated with carnosine or saline. Locomotor test, open field test, hot plate test, freezing test and Morris water maze were performed after rUCCAO. Results There were no differences among rUCCAO group, carnosine group and sham group for total distance traveled in lo-comotor test. In the open field test, carnosine (200, 500 mg · kg-1 ) significantly revised the decrease of latency spent in the center induced by SIVD . There were no differences between rUCCAO and sham groups for the pain threshold. In freezing test, rUCCAO in-duced a significant reduction in content memory, which was completely reversed by treatment of carnosine. In Morris water maze training trials, rUCCAO-treated mice showed prolonged escape latency in acquisition phase, carnosine ( 200, 500 mg · kg-1 ) markedly shortened the escape latency. Conclusion These data suggest that carnosine has a neuroprotective effect on cognitive impairment induced by rUCCAO in mice.

The Neuroprotective Effects of Carnosine in Early Stage of Focal Ischemia Rodent Model

OBJECTIVE: This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. METHODS: Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. RESULTS: Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. CONCLUSION: Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke.

Biological functions of histidine-dipeptides and metabolic syndrome

The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced glycoxidation/lipoxidation end products (AGEs/ALEs), resulting in cellular dysfunction. Therefore, an effective reactive carbonyl species and AGEs/ALEs sequestering agent may be able to prevent such cellular dysfunction. There is accumulating evidence that histidine containing dipeptides such as carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-methyl-L-histidine) detoxify cytotoxic reactive carbonyls by forming unreactive adducts and are able to reverse glycated protein. In this review, 1) reaction mechanism of oxidative stress and certain chronic diseases, 2) interrelation between oxidative stress and inflammation, 3) effective reactive carbonyl species and AGEs/ALEs sequestering actions of histidine-dipeptides and their metabolism, 4) effects of carnosinase encoding gene on the effectiveness of histidine-dipeptides, and 5) protective effects of histidine-dipeptides against progression of metabolic syndrome are discussed. Overall, this review highlights the potential beneficial effects of histidine-dipeptides against metabolic syndrome. Randomized controlled human studies may provide essential information regarding whether histidine-dipeptides attenuate metabolic syndrome in humans.

Prevention effect of carnosine on radiation-induced lung injury in mice / 中华放射医学与防护杂志

Objective To investigate the protective effect of carnosine on radiation-induced lung injury in mice.Methods A total of 108 C57/BL female mice were randomly divided into 4 groups:control group without treatment,irradiation alone group,irradiation + carnosine group (15 mg·kg-1·d-1),and carnosine alone group (15 mg· kg-1· d-1).There were 18 mice in control group and 30 mice in every other group.Whole lung anterior chest was irradiated with a single dose of 13 Gy 10 MV X-rays.The mice were administered with carnosine (15 mg· kg-1· d-1) at 30 minutes before irradiation and then garaged once a day until the end of the experiment.The control group was given with saline.At 7,28,and 56 d after irradiation,6 mice of control group and 10 mice of each other group were killed.A portion of lung tissues were stained with HE and other part of lung tissues were used to detect the levels of SOD.Meanwhile,TGF-β1 and TNF-α in the serum were detected with ELISA.Results Different levels of inflammation factors were expressed in the lung tissues of irradiation group and irradiation + carnosine group at 56 d after irradiation,but the inflammation in the irradiation + carnosine group was significantly lighter than that in the irradiation group.Among (7,28 and 56 d) after radiation,TGF-β1,TNF-α,and SOD levels in different groups had significant differences.At the same time point after irradiation,the level of SOD in lung tissue of irradiation + carnosine group was significantly higher than that of irradiation group (F =4.33,4.19,3.34,P ＜0.05),but the levels of TGF-β1 and TNF-α in serum were reduced.Conclusions Carnosine can prevent and inhibit radiation-induced lung injury in mice by increasing SOD and reducing TGF-β1 and TNF-α.

Effects of alpha-lipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats

alpha-Lipoic acid and L-carnosine are powerful antioxidants and are often used as a health supplement and as an ergogenic aid. The objective of this study was to investigate the effects of alpha-lipoic acid and/or L-carnosine supplementation on antioxidant activity in serum, skin, and liver of rats and blood lipid profiles for 6 weeks. Four treatment groups received diets containing regular rat chow diet (control, CON), 0.5% alpha-lipoic acid (ALA), 0.25% alpha-lipoic acid + 0.25% L-carnosine (ALA + LC), or 0.5% L-carnosine (LC). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and lipid peroxidation products, malondialdehyde (MDA) concentrations, were analyzed in serum, skin, and liver. Blood lipid profiles were measured, including triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). Skin and liver SOD activities of the ALA and LC groups were higher than those of the CON group (P < 0.05), but serum SOD activity was higher only in the LC group compared to that in the CON group (P < 0.05). Additionally, only liver GSH-Px activity in the LC group was higher than that of the CON and the other groups. Serum and skin MDA levels in the ALA and LC groups were lower than those in the CON group (P < 0.05). Serum TG and TC in the ALA and ALA + LC groups were lower than those in the CON and LC groups (P < 0.05). The HDL-C level in the LC group was higher than that in any other group (P < 0.05). LDL-C level was lower in the ALA + LC and LC groups than that in the CON group (P < 0.05). Thus, alpha-lipoic acid and L-carnosine supplementation increased antioxidant activity, decreased lipid peroxidation in the serum, liver, and skin of rats and positively modified blood lipid profiles.