Inhibitory effects of N-acetyl-L-cysteine on brain inflammation in mice with periodontitis and Alzheimer’s disease / 西安交通大学学报(医学版)

【Objective】 To explore the effects of periodontitis on the brains of Alzheimer’s disease (AD) mice and the effects of N-acetyl-L-cysteine (NAC) on the periodontium and the brain of AD mice with experimental chronic periodontitis (CP). 【Methods】 Ten wild-type C57 mice were in the blank control group (Group C57), and another 40 3-month-old APP/PS1 transgenic mice were randomly divided into four groups: AD+CP group, AD+CP+NAC group, AD+NAC group, and AD group. The periodontitis model was established in mice in AD+CP group and AD+CP+NAC group by silk ligation. At the same time, mice in AD+CP+NAC group and AD+NAC group were injected with NAC (200 mg/kg). The height of alveolar bone loss was detected after 3 weeks, and the cell morphology of the hippocampus was observed. We determined the expression levels of NLRP3 inflammasome and amyloid-β (Aβ) in the hippocampus as well as the expression levels of interleukin (IL)-1β and IL-18 in the hippocampus and gums by ELISA. 【Results】 Compared with AD group, the height of alveolar bone loss in AD+CP group was higher (P<0.05), and the expression levels of IL-18 in the gum and IL-1β and NLRP3 in the hippocampus were increased significantly (P<0.05). In addition, compared with AD+CP group, the height of alveolar bone loss in AD+CP+NAC group was reduced significantly (P<0.05), the expression levels of IL-1β and IL-18 in the gum were reduced significantly (P<0.05) as well as the expression levels of IL-1β and Aβ in the hippocampus were reduced significantly (P<0.05). Compared with C57 group, the neurons in the hippocampus of AD+CP group were more loose and disordered, and the activation of microglia was increased, while the disarrangement of cells in AD+CP+NAC group was less than that in AD+CP group. 【Conclusion】 Periodontitis can aggravate brain inflammation in AD mice. NAC can effectively reduce alveolar bone resorption in AD mice caused by periodontitis as well as reduce the levels of inflammatory factors in the gum and hippocampus. NAC can effectively reduce the alveolar bone absorption of AD mice caused by periodontitis, reduce the level of inflammatory factors in the gingiva and hippocampus, and reduce the damage of nerve cells in the hippocampus.

The Effect of Dietary Supplement on Glutathione Level in Rats

Background: Oxidative stress occurs due to decreased glutathione inside the body. Some supplements may promote and stimulate glutathione production in the liver. This article aims to investigate the impact of different supplements on enhancing glutathione synthesis in rats’ livers. For this purpose 42 rats (male albino) were separated into 7 groups, each including 6 animals with average weights ranging between 150 and 160 g. Group 1 (control) and different groups consumed a basal diet for 8 weeks, whereas group 2 received 500 mg/kg bw of L-cysteine daily. Group 3 received 250 mg/kg bw of methionine, while group 4 got 250 mg/kg of L cysteine plus 125 mg/kg of methionine daily. Spirulina (20 mg/kg bw), turmeric (500 mg/kg bw), and dried garlic (500 mg/kg bw), respectively, were given to groups 5, 6, and 7. Results: Utilizing the various dietary supplements decreased levels of liver function enzymes, bilirubin, urea, creatinine, and malondialdehyde while enhancing levels antioxidant enzymes of liver, and increased glutathione of kidneys and liver. However, cysteine alone at 500 mg/kg bw decreased glutathione formation in the liver and kidneys. Compared to the amino acid supplements (group 2, 3, 4) used, spirulina, turmeric, and dried garlic had a significant impact on reducing liver function enzymes, bilirubin, uric acid, creatinine, urea, and malondialdehyde and increasing antioxidant enzymes, and glutathione while turmeric supplement showed the best influence. Using dietary supplements did not result in any pathological modifications in the liver tissues, but there were some unsatisfactory minor alterations. However, group 2 showed considerable pathological developments in the liver tissues. Conclusion: According to the findings, using the suggested dietary supplement except for cysteine alone can promote and encourage glutathione synthesis in different organs, especially the liver, hence alleviating the effects of oxidative stress associated with several illnesses.

Associations of morning urinary 1-bromopropane metabolite with peripheral blood parameters in a community-based population / 环境与职业医学

Background As an environmental pollutant, 1-bromopropane (1-BP) is ubiquitous in the living environment. However, its health effects on the general population are still unclear. Objective To assess the associations between urinary 1-BP metabolite and blood routine indices in a Chinese community population. Methods A total of 3512 community residents aged 18-80 years from the baseline of the Wuhan-Zhuhai cohort were included in our study. The demographic characteristics, disease history, and lifestyles of the participants were collected through questionnaires. Height, weight, blood pressure, and other anthropometrics were collected through physical examination. Blood routine indicators were tested using an automated hematology analyzer. Urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-L-cysteine (BPMA) was measured by ultra-high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Generalized linear models and logistic regression models were used to assess the associations of urinary BPMA with blood routine indices and the risks of abnormal blood routine indices, respectively. Besides, stratified analysis and effect modification analysis were further conducted to investigate the effects of individual characteristics and lifestyles on the associations of urinary BPMA with blood routine indices. All models were adjusted for gender, age, and other potential confounders. Results The mean age of the study population (30.1% male) was (52.78±12.77) years. The median (P25, P75) level of urinary BPMA adjusted for urinary creatinine was 0.90 (0.50, 1.73) mg·mol−1. In the analysis with target indicator as continuous variable, each 1-unit increase in natural logarithm-transformed urinary BMPA level was associated with a 0.078×109 L−1, 0.031×109 L−1, 0.307%, 3.518 g·L−1, and 2.469×109 L−1 decrease in white blood cell, lymphocyte, lymphocyte percentage, mean corpuscular hemoglobin concentration, and platelet levels, respectively (all Ps<0.05); and with a 0.440%, 1.140 fL, 0.014 fL, and 0.020 increase in hematocrit, mean corpuscular volume, and natural logarithm-transformed levels of mean platelet volume and mean platelet volume/platelet, respectively (all Ps<0.05). The categorical analysis across quartiles of BPMA level showed that BPMA was inversely associated with lymphocyte percentage, mean corpuscular hemoglobin concentration, and platelet levels in a dose-dependent manner (all Ptrend<0.05), and positively related to hematocrit, mean corpuscular volume, mean platelet volume, and mean platelet volume/platelet levels in a dose-dependent manner (all Ptrend<0.05). Body mass index, smoking, and drinking modified the associations of urinary BPMA level with red blood cell, mean corpuscular hemoglobin concentration lymphocyte percentage, and hemoglobin (all Ps<0.05). In addition, urinary BPMA was associated with an increased risk of abnormal increase in mean corpuscular volume (OR=1.316, 95%CI: 1.171-1.478) and red blood cell volume distribution width (OR=1.255, 95%CI: 1.030-1.528), and abnormal decrease in mean corpuscular hemoglobin concentration (OR=1.200, 95%CI: 1.035-1.392). Conclusion Exposure to 1-BP of the general population is associated with decreased white blood cells and platelets, as well as abnormal change of blood cell morphology or function.

Construction of an l-cysteine hyper-producing strain of Escherichia coli based on a balanced carbon and sulfur module strategy / 生物工程学报

l-cysteine is an important sulfur-containing α-amino acid. It exhibits multiple physiological functions with diverse applications in pharmaceutical cosmetics and food industry. Here, a strategy of coordinated gene expression between carbon and sulfur modules in Escherichia coli was proposed and conducted for the production of l-cysteine. Initially, the titer of l-cysteine was improved to (0.38±0.02) g/L from zero by enhancing the biosynthesis of l-serine module (serAf, serB and serCCg) and overexpression of CysB. Then, promotion of l-cysteine transporter, increased assimilation of sulfur, reduction or deletion of l-cysteine and l-serine degradation pathway and enhanced expression of cysEf (encoding serine acetyltransferase) and cysBSt (encoding transcriptional dual regulator CysB) were achieved, resulting in an improved l-cysteine titer (3.82±0.01) g/L. Subsequently, expressions of cysM, nrdH, cysK and cysIJ genes that were involved in sulfur module were regulated synergistically with carbon module combined with utilization of sulfate and thiosulfate, resulting in a strain producing (4.17±0.07) g/L l-cysteine in flask shake and (11.94±0.1) g/L l-cysteine in 2 L bioreactor. Our results indicated that efficient biosynthesis of l-cysteine could be achieved by a proportional supply of sulfur and carbon in vivo. This study would facilitate the commercial bioproduction of l-cysteine.

Protective effect of N-acetyl-L-cysteine and rosuvastatin against oxidative stress in fibroblasts from asymptomatic patients with X-ALD: a preliminary study

Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV. Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples. Conclusions: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease. (AU)

Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.

Establishment of ocular apoptosis model in zebrafish / 中国药理学通报

To establish a model of ocular apoptosis in zebrafish by using dibutyl phthalate(DBP), and accordingly to evaluate the activity of anti-ocular apoptosis drugs. Methods Zebrafish embryos (30 hpf) were treated with DBP(0. 1, 10, 50, 100 jxmol L " 1) for 18 h and 42 h, and the survival rate was calculated. Then zebrafish embryos (30 or 54 hpf) were incubated with DBP(0. 1, 1 , 5 , 10, 50 |j.mol L 1) for 18 h under direct or indirect light conditions, and visualized under microscope, then the ocular apoptosis was assessed by AO staining. Furthermore, modeled zebrafish was treated with N-acetyl-L-cysteine(NAC) or ginsenoside Rgl, and the effects on ocular apoptosis were observed. Results There was no mortality in zebrafish at concentrations below 10 |j,mol L"1 after modeling with DBP for 18 h and 42 h. The survival rate of zebrafish was significantly reduced with a concentration above 50 |xmol L"1 (P < 0 . 0 1) . Furthermore, obvious ocular apoptosis was found at 30 hpf after 18 h with DBP(10 (unol L"1) (P < 0. 0 1) . The zebrafish showed spontaneous apoptosis of the ocular cells at 72 h, which was not associated with light conditions. Effect of NAC or ginsenoside Rgl was observed on decreasing ocular apoptosis in zebrafish (P < 0. 05) . Conclusions DBP can be used to rapidly and efficiently establish a model of ocular apoptosis in zebrafish, which can be used for rapid evaluation of drug activity-.

Effect of N-acetyl-L-cysteine on bioavailability and brain distribution of curcumin by nasal delivery / 中国中药杂志

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.

Antioxidants in the control of microorganism contamination and phenol oxidation in Eugenia pyriformis / Antioxidantes no controle da contaminação microbiana e da oxidação fenólica em Eugenia pyriformis

Uvaia (Eugenia pyriformis) is a fruit tree of the Myrtaceae family. It has recalcitrant seeds of limited longevity, making seed propagation difficult. Micropropagation is an alternative method to obtain a large quantity of progeny plants in a short period of time, by using any part of the plant as explant. The high concentration of phenols associated with the chemical composition of the Myrtaceae, and the presence of microorganisms in the plant material or culture media, can make in vitro propagation difficult and/or impossible. The objective was to evaluate various concentrations of antioxidants affecting the control of microbial contamination and phenol oxidation in vitro in uvaia. A completely randomized design was used, with a 3 (antioxidants PVP, L-cysteine, and ascorbic acid) × 3 (antioxidant concentrations 100, 200, and 300 mg L-1) × 2 (activated charcoal at 0 and 2 g L-1) factorial arrangement + 2 additional variables (absence of antioxidants and activated charcoal; absence of antioxidants with 2 g L-1 activated charcoal), with three repetitions comprising four plants each. The percentage of bacterial and fungal contaminations, along with the number of oxidized explants, was evaluated after 7, 14 and 21 days of in vitro cultivation. It was concluded that, where bacterial and fungal contaminations were concerned, in vitro cultivation of uvaia can be performed without the use of antioxidants. PVP or ascorbic acid must, however be used in the process, at a concentration of 300 mg L-1, along with 2 g L-1 of activated charcoal. This helps to minimize phenol oxidation.

A uvaia Eugenia pyriformis é uma frutífera da família das mirtáceas cujas sementes apresentam longevidade curta e aspecto recalcitrante, fato que dificulta a propagação seminífera. A micropropagação surge como alternativa para obtenção de grande quantidade de mudas em curto período de tempo, por meio da utilização de qualquer parte da planta como explante. A elevada concentração de fenóis associados à composição química das mirtáceas e a presença de microrganismos no material vegetal ou no meio de cultura podem dificultar e/ou impossibilitar a propagação in vitro. Objetivou-se avaliar tipos e concentrações de antioxidantes no controle da contaminação microbiana e da oxidação fenólica in vitro de E. pyriformis. Utilizou-se o delineamento inteiramente casualizado em esquema fatorial 3 (antioxidantes ­ PVP, L-cisteína e ácido ascórbico) x 3 (concentrações - 100, 200 e 300 mg L-1) x 2 (carvão ativado ­ 0 e 2 g L-1) + 2 adicionais (ausência de antioxidantes e de carvão ativado; ausência de antioxidantes com 2 g L-1 de carvão ativado), com três repetições constituídas por quatro plantas. Após sete, 14 e 21 dias do cultivo in vitro foram avaliadas a porcentagem de contaminação bacteriana, fúngica e de explantes oxidados. Conclui-se que o cultivo in vitro de E. pyriformis, em relação as contaminações bacterianas e fúngicas, pode ser efetuado sem a utilização de agentes antioxidantes. Entretanto, para reduzir a oxidação fenólica deve ser utilizado o PVP ou ácido ascórbico, ambos na concentração de 300 mg L-1, associados a 2 g L-1 de carvão ativado.

Protective effects of N-acetyl-L-cysteine against binge drinking-induced fatty liver in mice / 中华劳动卫生职业病杂志

Objective@#To investigate the roles of N-acetyl-L-cysteine (NAC) against binge drinking-induced fatty liver in mice.@*Methods@#SPF male C57BL/6 mice were randomly divided into 3 groups, i.e. control group, model group, and NAC/ethanol group (n=10). Mice in model and NAC/ethanol groups were exposed to 3 doses of ethanol (6 g/kg bw) to induced fatty liver, while mice in control group received equal volume and equal energy of maltodextrin solution. NAC was administered to mice at 1 h before ethanol exposure (100 mg/kg bw, i.p.). The mice were sacrificed at 6 h after the last ethanol exposure. The liver and epididymal adipose tissues were collected. Histopathological examination and biochemical assay kit were used to evaluate the fat accumulation, while Western-blot was performed to detect the protein levels of some key factors involved in fat metabolism in liver and adipose tissues.@*Results@#Compored with control group mice, the liver index and liver weight were significantly increased compared with model group, the liver index and TG level in NAC/ethanol group mice were all significantly decreased (P<0.05). Histological examination showed NAC effectively suppressed binge drinking-induced fat accumulation in mice liver. In addition, NAC had no significant effects on the protein levels of peroxisome proliferator-activated receptor-α (PPAR-α), Acy-CoA oxidase (ACOX), sterol regulatory element binding protein 1 c (SREBP-1c) and fatty acid synthase (FAS). Furthermore, the protein levels of hormone sensitive lipase (HSL) did not significantly differ among 3 groups, whereas NAC prevented binge drinking-induced increase of HSL phosphorylation at ser563 and ser660.@*Conclusion@#NAC could effectively attenuate binge drinking-induced fatty liver, which might be associated with the inhibition of lipid mobilization by suppressing the phosphorylation of HSL.

DNA damage in homocystinuria: 8-oxo-, 8-dihydro-2'-deoxyguanosine levels in cystathionine-ß-synthase deficient patients and the in vitro protective effect of N-acetyl­L­cysteine

Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine ß-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBS­deficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2'- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 µM and 200 µM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria.

The long and successful journey of electrochemically active amino acids. From fundamental adsorption studies to potential surface engineering tools

ABSTRACT Proteins have been the subject of electrochemical studies. It is possible to apply electrochemical techniques to obtain information about their structure due to the presence of five electroactive amino acids that can be oriented to the outside of the peptidic chain. These amino acids are L-Tryptophan (L-Trp), L-Tyrosine (L-Tyr), L-Histidine (L-His), L-Methionine (L-Met) and L-Cysteine (L-Cys); their electrochemical behavior being subject of extensive research, but it is still controversial. No spectroscopic investigations have been reported on L-Trp, and due to the short life time of the intermediates, ex situ techniques cannot be employed, leading to a never-ending discussion about possible intermediates. In the L-Tyr and L-His cases, spectroelectrochemical studies were performed and different intermediates were observed, suggesting that some intermediates may be observed under specific conditions, as proposed for L-Cys. This amino acid is the most interesting among the electroactive ones because of the presence of a thiol moiety at its side chain, leading to a wide range of oxidation states. It can adsorb onto surfaces of different crystallographic orientation in stereoselective conformation, modifying the surface for different applications.as a surface engineering tool since it plays the role of as an anchor for the growing of nanocrystals inside proteic templates.

Research progress on major pharmacological activities of S-allyl-L-cysteine / 国际生物医学工程杂志

Oxidation and inflammation are associated with the pathological processes of most human diseases, posing a serious threat to human health. In recent years, researchers have extracted monomeric compounds from natural products for the prevention and treatments of diseases related to oxidation and inflammation. That has become a major trend in the study of anti-oxidant and anti-inflammatory drugs. Garlic, a natural product, has pharmacological activities such as anti-tumor, anti-inflammatory and detoxification and so on. Therefore, it is important to study and extract the active ingredients in garlic. As an active ingredient extracted from garlic, S-allyl-L-cysteine (SAC) has been extensively studied in cell and animal models. The main pharmacological activities of SAC and the related receptors were reviewed, and its mechanism of action in vivo and the beneficial effects on the corresponding diseases were summarized to provide the necessary basis for further study.

Ultrasensitive Determination of L-Cysteine Based on Its Enhancement to Electrochemiluminescence of CdS Quantum Dots with Cd2+Rich Surface / 分析化学

A novel electrochemiluminescence ( ECL) method for the determination of L-cysteine ( L-Cys) was established. water-soluble CdS quantum dots ( QDs) with Cd2+rich surface were synthesized via a controllable one-poe approach. The mercapto group in L-cysteine molecule can specifically interact with excessive Cd2+on the surface of CdS QDs, resulting in enhancement of ECL intensity of the CdS QDs, which can be used for the detection of L-Cys. Under the optimal experimental conditions, the enhancement of ECL intensity was linear with the concentration of L-Cys in the range of 5. 0×10-9-1. 0×10-5 mol/L. The limit detection of (S/N=3) was 1. 2×10-9 mol/L. In comparison with other methods for detecting L-Cys, this method is more simple and selective, and can be applied to detect L-Cys in real sample with satisfactory results.

Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.

In vitro effect of N-acetyl-L-cysteine on glutathione and sulfhydryl levels in X-linked adrenoleukodystrophy patients

Introduction: Recent evidence shows that oxidative stress seems to be related with the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), a neurodegenerative disorder. Methods: In the present study, the in vitro effect of N-acetyl-L-cysteine (NAC) on glutathione (GSH) and sulfhydryl levels in X-ALD patients was evaluated. Results: A significant reduction of GSH and sulfhydryl content was observed in X-ALD patients compared to the control group. Furthermore, 5 mM of NAC, in vitro, led to an increase in GSH content and sulfhydryl groups in these patients. Conclusion: These data probably indicate that an adjuvant therapy with the antioxidant NAC could improve the oxidative imbalance in X-ALD patients(AU)

Preventive and therapeutic effect of N-Acetyl-l-cysteine on infection-associated preterm labor in mice

OBJECTIVE@#To study the preventive and therapeutic effect of N-Acetyl-l-cysteine on infection-associated preterm labor in mice.@*METHODS@#A total of 66 C57BL/6 inbred strain pregnant mice were selected and randomly divided into groups A, B and C, with 22 cases in each group. Group A, B and C were regarded as model group, prevention group and treatment group, respectively. The model of infection-associated preterm labor was built by intraperitoneal injection of Escherichia coli. Ten mice of each group were taken and observed the preterm birth rates and live birth rates, respectively. Three mice of each group were killed at 3 h, 6 h, 12 h and 24 h after building the model. Their uterus tissues were collected and the expressions of the AP-1 and MCP-1 in those tissues were assayed with immunohistochemical method and the expressions of NF-κBp65 and TNF-α protein in the placenta tissues of those mice were also detected with immunohistochemical method.@*RESULTS@#The preterm birth rates of mice in groups B and C were significantly lower than that in group A, while their live birth rates were distinctly higher than that in group A (P  0.05).@*CONCLUSIONS@#N-Acetyl-l-cysteine can lower the incidence rate of infection-associated preterm labor by prohibiting the activation of the protein AP-1/MCP-1 and decreasing the expression of NF-κBp65 and TNF-α in the pregnant tissues of premature mice to reduce the inflammatory reactions.

PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. METHODS: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. RESULTS: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. CONCLUSIONS: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.

Preventive and therapeutic effect of N-Acetyl-l-cysteine on infection-associated preterm labor in mice

Objective: To study the preventive and therapeutic effect of N-Acetyl-. l-cysteine on infection-associated preterm labor in mice. Methods: A total of 66 C57BL/6 inbred strain pregnant mice were selected and randomly divided into groups A, B and C, with 22 cases in each group. Group A, B and C were regarded as model group, prevention group and treatment group, respectively. The model of infection-associated preterm labor was built by intraperitoneal injection of Escherichia coli. Ten mice of each group were taken and observed the preterm birth rates and live birth rates, respectively. Three mice of each group were killed at 3 h, 6 h, 12 h and 24 h after building the model. Their uterus tissues were collected and the expressions of the AP-1 and MCP-1 in those tissues were assayed with immunohistochemical method and the expressions of NF-κBp65 and TNF-α protein in the placenta tissues of those mice were also detected with immunohistochemical method. Results: The preterm birth rates of mice in groups B and C were significantly lower than that in group A, while their live birth rates were distinctly higher than that in group A (P 0.05). Conclusions: N-Acetyl-. l-cysteine can lower the incidence rate of infection-associated preterm labor by prohibiting the activation of the protein AP-1/MCP-1 and decreasing the expression of NF-κBp65 and TNF-α in the pregnant tissues of premature mice to reduce the inflammatory reactions.

N-acetyl-L-cysteine and cysteine increase intracellular calcium concentration in human neutrophils

N-acetyl-L-cysteine (NAC) and cysteine have been implicated in a number of human neutrophils' functional responses. However, though Ca²⁺ signaling is one of the key signalings contributing to the functional responses of human neutrophils, effects of NAC and cysteine on intracellular calcium concentration ([Ca²⁺]ᵢ) in human neutrophils have not been investigated yet. Thus, this study was carried out with an objective to investigate the effects of NAC and cysteine on [Ca²⁺]ᵢ in human neutrophils. We observed that NAC (1 µM ~ 1 mM) and cysteine (10 µM ~ 1 mM) increased [Ca²⁺]ᵢ in human neutrophils in a concentration-dependent manner. In NAC pre-supplmented buffer, an additive effect on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced increase in [Ca²⁺]ᵢ in human neutrophils was observed. In Ca²⁺-free buffer, NAC- and cysteine-induced [Ca²⁺]ᵢ increase in human neutrophils completely disappeared, suggesting that NAC- and cysteine-mediated increase in [Ca²⁺]ᵢ in human neutrophils occur through Ca²⁺ influx. NAC- and cysteine-induced [Ca²⁺]ᵢ increase was effectively inhibited by calcium channel inhibitors SKF96365 (10 µM) and ruthenium red (20 µM). In Na⁺-free HEPES, both NAC and cysteine induced a marked increase in [Ca²⁺]ᵢ in human neutrophils, arguing against the possibility that Na⁺-dependent intracellular uptake of NAC and cysteine is necessary for their [Ca²⁺]ᵢ increasing activity. Our results show that NAC and cysteine induce [Ca²⁺]ᵢ increase through Ca²⁺ influx in human neutrophils via SKF96365- and ruthenium red-dependent way.