advanced glycation end products

糖基化终产物
  • 文章类型: Journal Article
    晚期糖基化终产物(AGEs)是通过美拉德反应形成的,在烹饪中广泛发生的非酶过程,食品加工,在人体内。首先,AGEs是由氨基还原糖的糖基化形成的,这个过程是依赖于热量的。随着生活方式的改变,饮食习惯的多样性有所增加,包括那些与西方饮食有关的模式,其中包括食用富含AGEs的加工食品。已知过量摄入和暴露于AGEs会导致身体功能异常,如肥胖,糖尿病,脂肪肝,以及AGEs在食品加工中对改善食品风味和质量的有益作用。为了获得关于各种食物和人类样本中的AGEs的有意义的数据,有必要更精确地表征和分析从样品中提取的AGEs以获得准确的结果。这篇综述探讨了食品中AGEs的最新分析研究和表征,包括酪蛋白,β-乳球蛋白,大豆蛋白,和肉类蛋白质,在人体样本中,如糖化白蛋白,血红蛋白,和等离子体。此外,它探讨了体内AGEs的代谢命运以及与代谢异常相关的疾病的机制,这些代谢异常可能是由食用含有AGEs的食物引起的。这篇综述旨在概述由含有AGEs的食物或体内产生的AGEs引起的代谢异常的相关近期和未来研究的观点。
    Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat-dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, β-lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated-albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body.
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  • 文章类型: Journal Article
    在不同人群中,一些心血管危险指标与睡眠时间的改变有关;然而,在健康人群中几乎没有证据。
    本研究的目的是分析睡眠持续时间与心血管风险生物标志物之间的关联,包括通过皮肤自发荧光(SAF)测量的晚期糖基化终产物(AGEs),最大颈动脉内中膜厚度(IMTMax),主动脉脉搏波传导速度(a-PWV),脉压(PP),低密度脂蛋白胆固醇(LDL-C),健康成人(EVasCu研究)。
    EVasCu研究包括390名参与者。在睡眠持续时间和心血管风险标志物之间进行简单和多重线性回归。然后在将睡眠分类为6小时后,进行针对各种协变量进行校正的ANOVA分析和ANCOVA分析。6-8小时,>8小时。
    296名参与者被纳入分析(43.97±12.60岁,63.9%女性)。简单的线性回归显示睡眠持续时间与SAF之间呈负相关,IMTMax,aPWV和PP。然而,在具有所有协变量的多元线性回归中,失去了统计学意义。就其本身而言,在方差分析中,睡眠持续时间也与相同的参数相关,但是当执行完全调整后的ANCOVA分析时,SAF的统计显著性保持不变(p=0.015),当比较<6h组与比较时,获得0.223任意单位的差异(p=0.017)>8小时。最后,LDL-C没有关联。
    在睡眠持续时间和APS之间发现了负相关,这被认为是心血管风险的标志。虽然需要前瞻性研究,有人认为睡眠不足可能会增加心血管风险,这可能是未来促进健康和预防心血管疾病的公共卫生政策的关键因素。
    UNASSIGNED: Some cardiovascular risk markers have been associated with alterations in sleep duration in different populations; however, there is little evidence in a healthy population.
    UNASSIGNED: The aim of the present study was to analyze the associations between sleep duration and cardiovascular risk biomarkers, including advanced glycation end-products (AGEs) measured by skin autofluorescence (SAF), maximum carotid intima-media thickness (IMTMax), aortic pulse wave velocity (a-PWV), pulse pressure (PP), and low-density lipoprotein cholesterol (LDL-C), in healthy adults (EVasCu study).
    UNASSIGNED: The EVasCu study included 390 participants. Simple and multiple linear regressions were performed between sleep duration and cardiovascular risk markers. ANOVA analysis and ANCOVA analysis adjusted for various covariates were then performed after categorizing sleep into 6 h, 6-8 h, and >8 h.
    UNASSIGNED: 296 participants were included in the analyses (43.97 ± 12.60 years, 63.9% female). Simple linear regressions showed an inverse association between sleep duration and SAF, IMTMax, aPWV and PP. However, in the multiple linear regression with all the covariates, the statistical significance was lost. For its part, in the ANOVA analyses, sleep duration was also associated with the same parameters, but when performing the fully adjusted ANCOVA analyses, the statistical significance for SAF was maintained (p = 0.015), obtaining a difference of 0.223 arbitrary units (p = 0.017) when comparing the group <6 h vs. > 8 h. Finally, there was no association for LDL-C.
    UNASSIGNED: An inverse association was found between sleep duration and APS, which is considered a marker of cardiovascular risk. Although prospective studies are needed, it is suggested that insufficient sleep may increase cardiovascular risk, which could be a key factor in future public health policies to promote health and prevent CVD.
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  • 文章类型: Journal Article
    晚期糖基化终产物(AGEs)是主要在糖尿病(DM)中增加的细胞毒性化合物,肾衰竭,炎症,以及对摄入富含AGE的饮食的反应。AGEs还可以通过降低Slc2a4(溶质载体家族2成员4)基因及其GLUT4(溶质载体家族2,促进葡萄糖转运蛋白成员4)蛋白在肌肉中的表达来损害血糖稳态。然而,AGE对脂肪细胞影响的潜在机制尚未得到证实。这项研究调查了AGEs对3T3-L1脂肪细胞Slc2a4/GLUT4表达的影响,以及NFKB(核因子NF-κB)活性在观察到的作用中的潜在作用。将脂肪细胞在浓度为0.4、3.6和5.4mg/mL的对照白蛋白(CA)或晚期糖化白蛋白(GA)存在下培养24小时或72小时。Slc2a4,Rela,通过RT-qPCR检测Nfkb1mRNA,GLUT4,IKKA/B,和p50/p65NFKB亚基使用蛋白质印迹,通过染色质免疫沉淀(ChIP)测定分析p50/p65与Slc2a4启动子的结合。0.4mg/mL的GA在24小时和72小时后增加了Slc2a4/GLUT4的表达(从50%到100%),但在5.4毫克/毫升时,Slc2a4/GLUT4表达在72h时下降(下降50%)。在所有浓度下,Rela和Nfkb1表达在24小时后增加,但在72小时没有观察到这种效果。此外,5.4mg/mL的GA在72h时增加了p50/p65核含量并结合到Slc2a4中。总之,这项研究揭示了AGE诱导的和NFKB介导的Slc2a4/GLUT4表达的抑制。这可能会损害脂肪细胞葡萄糖的利用,不仅导致DM受试者血糖控制恶化,而且在高摄入富含AGE的食物下,非DM受试者的血糖稳态受损。
    Advanced glycated end products (AGEs) are cytotoxic compounds that are mainly increased in diabetes mellitus (DM), kidney failure, inflammation, and in response to the ingestion of AGE-rich diets. AGEs can also impair glycemic homeostasis by decreasing the expression of the Slc2a4 (solute carrier family 2 member 4) gene and its GLUT4 (solute carrier family 2, facilitated glucose transporter member 4) protein in muscle. However, the mechanisms underlying AGE\'s effect on adipocytes have not been demonstrated yet. This study investigated the effects of AGEs upon Slc2a4/GLUT4 expression in 3T3-L1 adipocytes, as well as the potential role of NFKB (nuclear factor NF-kappa-B) activity in the effects observed. Adipocytes were cultured in the presence of control albumin (CA) or advanced glycated albumin (GA) at concentrations of 0.4, 3.6, and 5.4 mg/mL for 24 h or 72 h. Slc2a4, Rela, and Nfkb1mRNAs were measured by RT-qPCR, GLUT4, IKKA/B, and p50/p65 NFKB subunits using Western blotting, and p50/p65 binding into the Slc2a4 promoter was analyzed by chromatin immunoprecipitation (ChIP) assay. GA at 0.4 mg/mL increased Slc2a4/GLUT4 expression after 24 h and 72 h (from 50% to 100%), but at 5.4 mg/mL, Slc2a4/GLUT4 expression decreased at 72 h (by 50%). Rela and Nfkb1 expression increased after 24 h at all concentrations, but this effect was not observed at 72 h. Furthermore, 5.4 mg/mL of GA increased the p50/p65 nuclear content and binding into Slc2a4 at 72 h. In summary, this study reveals AGE-induced and NFKB-mediated repression of Slc2a4/GLUT4 expression. This can compromise the adipocyte glucose utilization, contributing not only to the worsening of glycemic control in DM subjects but also the impairment of glycemic homeostasis in non-DM subjects under the high intake of AGE-rich foods.
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  • 文章类型: Journal Article
    这项研究的目的是评估地中海饮食(MD)与通过皮肤自发荧光测量的晚期糖基化终产物(AGEs)积累之间的关联。这项横断面研究包括来自斯普利特大学的1016名健康学生,克罗地亚。参与者完成了一份自我管理的问卷。使用地中海饮食服务评分(MDSS)评估对MD的依从性,和组织AGEs积累使用AGE阅读器mu(诊断光学)测量。分析采用多元线性回归。学生的年龄和女性性别与较高的AGEs水平相关,这同样被发现有更多的咖啡摄入量,充足的橄榄油消费,吸烟,和较低水平的体力活动。较高的蔬菜消耗和定期吃早餐与较低的AGEs水平有关。总体MD依从性与AGEs无关,可能是由于学生对MD原则的总体依从性非常低(女性为8.3%,男性为3.8%)。健康感知与MD和不吸烟呈正相关,与感知的压力水平呈负相关。而AGEs与自评学生的健康状况没有显着关联。这些结果表明,即使在年轻人和一般健康人中,各种生活习惯也与AGEs积累有关。因此,从小就有必要采取健康促进和预防措施。
    The aim of this study was to evaluate the association between the Mediterranean diet (MD) and the accumulation of advanced glycation end products (AGEs) measured by skin autofluorescence. This cross-sectional study included 1016 healthy students from the University of Split, Croatia. Participants completed a self-administered questionnaire. Adherence to the MD was assessed using the Mediterranean Diet Serving Score (MDSS), and tissue AGEs accumulation was measured using the AGE Reader mu (DiagnOptics). Multivariate linear regression was used in the analysis. Students\' age and female gender were associated with higher levels of AGEs, which was likewise found for greater coffee intake, adequate olive oil consumption, smoking, and lower levels of physical activity. Higher consummation of vegetables and eating breakfast regularly were associated with lower AGEs levels. The overall MD adherence was not associated with AGEs, possibly due to very low overall compliance to the MD principles among students (8.3% in women and 3.8% in men). Health perception was positively associated with the MD and nonsmoking and negatively with the perceived stress level, while AGEs did not show significant association with self-rated students\' health. These results indicate that various lifestyle habits are associated with AGEs accumulation even in young and generally healthy people. Hence, health promotion and preventive measures are necessary from an early age.
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  • 文章类型: Journal Article
    本研究旨在研究源自Sesuvioides植物的新天然化合物在减轻糖尿病小鼠模型中的糖尿病症状和胰岛素抵抗中的作用。抗晚期糖基化活性,胰岛素,通过酶联免疫吸附测定(ELISA)定量和脂联素。使用酶荧光测定法进行葡萄糖摄取,使用PAS染色测量糖原合成。使用实时PCR(RT-PCR)评估基因和蛋白质表达,免疫印迹和荧光显微镜,分别。从S.sesuvioides中分离的新的类黄酮糖苷eupalitin3-O-α-L-鼠李糖吡喃-(1→2)-β-D-吡喃葡萄糖苷1通过减少肝细胞中的人糖化白蛋白而表现出抗AGE活性。在用化合物1治疗的糖尿病小鼠模型中,我们观察到葡萄糖耐量改善,脂联素水平升高,胰岛素抵抗降低。我们还在化合物1处理的糖尿病小鼠肌肉中观察到缓解的AGEs诱导的葡萄糖摄取减少和糖原合成恢复。探讨糖尿病小鼠骨骼肌组织的分子作用机制,我们发现1减少了糖尿病小鼠肌肉中AGE诱导的活性氧和炎症基因。此外,图1所示的实施例通过降低晚期糖基化终产物(RAGE)受体的基因和蛋白质表达并抑制蛋白激酶C(PKC)δ活化而表现出这些作用。这进一步导致我们证明化合物1降低IRS-1的丝氨酸磷酸化,从而恢复胰岛素敏感性。我们得出的结论是,来自S.sesuvioides的一种新的类黄酮糖苷可能是治疗胰岛素抵抗和糖尿病症状的治疗靶标。
    The current study intended to investigate the role of new natural compounds derived from the Sesuvium sesuvioides plant in mitigating symptoms of diabetes and insulin resistance in the diabetic mice model. Anti-advanced glycation activity, insulin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Glucose uptake was performed using enzymatic fluorescence assay, and glycogen synthesis was measured using PAS staining. Gene and protein expression was assessed using real time PCR (RT-PCR), and immunoblotting and fluorescent microscopy, respectively. The new flavonoid glycoside eupalitin 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside 1 isolated from S. sesuvioides exhibited anti-AGE activity by reducing human glycated albumin in liver cells. In a diabetic mouse model treated with compound 1, we observed improved glucose tolerance, increased adiponectin levels, and decreased insulin resistance. We also observed alleviated AGEs induced reduction in glucose uptake and restored glycogen synthesis in the compound 1-treated diabetic mice muscles. Exploring the molecular mechanism of action in skeletal muscle tissue of diabetic mice, we found that 1 reduced AGE-induced reactive oxygen species and the inflammatory gene in the muscle of diabetic mice. Additionally, 1 exhibited these effects by reducing the gene and protein expression of receptor for advanced glycation end products (RAGE) and inhibiting protein kinase C (PKC) delta activation. This further led us to demonstrate that compound 1 reduced serine phosphorylation of IRS-1, thereby restoring insulin sensitivity. We conclude that a new flavonoid glycoside from S. sesuvioides could be a therapeutic target for the treatment of symptoms of insulin resistance and diabetes.
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  • 文章类型: Journal Article
    八个化合物,包括一个蒽醌,两个双苄基,一个菲,三个二氢菲,和一种类黄酮,从多花石斛壁的根中分离出来。前Lindl.其中,研究了六个化合物对α-葡萄糖苷酶的抑制活性,α-淀粉酶,和糖基化终产物(AGEs)的生产。此外,进行分子对接以分析测试化合物与α-葡萄糖苷酶的相互作用。摩司他汀,唯一分离的菲,显示最强的抗α-葡萄糖苷酶活性,IC50为32.45±1.04μM,大约比阿卡波糖小10倍。此外,moscatilin最强烈地抑制α-淀粉酶和AGEs的产生,IC50值为256.94±9.87和67.89±9.42μM,分别。分子对接分析显示所有物质与α-葡萄糖苷酶的有效结合具有比阿卡波糖更小的最低结合能值。选择莫司他进行动力学研究,它被鉴定为非竞争性抑制剂,其抑制能力比阿卡波糖高约9倍。这项研究代表了有关源自D.polyanthumWall根的化合物的植物化学成分和抗糖尿病潜力的第一份报告。前Lindl.
    Eight compounds, including one anthraquinone, two bibenzyls, one phenanthrene, three dihydrophenanthrenes, and one flavonoid, were isolated from the roots of Dendrobium polyanthum Wall. ex Lindl. Among these, six compounds were investigated for inhibitory activities against alpha-glucosidase, alpha-amylase, and advanced glycation end products (AGEs) production. Additionally, molecular docking was conducted to analyze the interactions of the test compounds with alpha-glucosidase. Moscatin, the only isolated phenanthrene, displayed the strongest anti-alpha-glucosidase activity with an IC50 of 32.45 ± 1.04 μM, approximately 10-fold smaller than that of acarbose. Furthermore, moscatilin most strongly inhibited alpha-amylase and AGEs production with IC50 values of 256.94 ± 9.87 and 67.89 ± 9.42 μM, respectively. Molecular docking analysis revealed the effective binding of all substances to alpha-glucosidase with smaller lowest binding energy values than acarbose. Moscatin was selected for kinetics studies, and it was identified as a non-competitive inhibitor with approximately 9-fold greater inhibitory capability than acarbose. This study represents the first report on the phytochemical constituents and antidiabetic potential of compounds derived from the roots of D. polyanthum Wall. ex Lindl.
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  • 文章类型: English Abstract
    OBJECTIVE: To clarify the role of advanced glycation end products (AGEs) and inflammation in the development of vascular calcification and cardiovascular complications at different stages of chronic kidney disease (CKD) G1-G5D.
    METHODS: We examined 105 patients aged 19 to 75 years with stage C1-C5D CKD, 77 (74%) of whom were patients with diabetic nephropathy. The concentration of AGEs, interleukin (IL)-1, IL-6 and tumor necrosis factor α (TNF-α), troponin I, parathyroid hormone was determined by enzyme-linked immunosorbent assay (ELISA) using kits from BluGene biotech (Shanghai, China), Cloud-Clone Corp. (USA), ELISA Kit (Biomedica, Austria).
    RESULTS: A high content of AGEs, IL-1, IL-6, TNF-α was established, which directly correlated with the increase in renal failure and changes in the morpho-functional parameters of the left ventricle and aorta.
    CONCLUSIONS: An increase in serum concentrations of AGEs and inflammatory mediators, correlating with a decrease in renal function and changes in the morpho- functional parameters of the left ventricle and aorta, indicate their significant role in the processes of damage to the cardiovascular system in CKD.
    Цель. Уточнить роль конечных продуктов гликирования (advanced glycation end products – AGEs) и воспаления в развитии сосудистой кальцификации и сердечно-сосудистых осложнений на разных стадиях хронической болезни почек (ХБП) – С1–С5Д. Материалы и методы. Обследованы 105 пациентов в возрасте от 19 до 75 лет с ХБП С1–С5Д-стадии, 77 (74%) из которых были больные с диабетической нефропатией. Концентрацию AGEs, интерлейкина (ИЛ)-1, ИЛ-6 и фактора некроза опухоли α (ФНО-α), тропонина I, паратиреоидного гормона определяли методом иммуноферментного анализа с применением наборов фирм BluGene biotech (Shanghai, Китай), Cloud-Clone Corp. (США), ELISA Kit (Biomedica, Австрия). Результаты. Установлено высокое содержание показателей AGEs, ИЛ-1, ИЛ-6, ФНО-α, прямо коррелировавших с нарастанием почечной недостаточности и изменениями морфофункциональных параметров левого желудочка и аорты. Заключение. Повышение сывороточных концентраций AGEs и медиаторов воспаления, коррелирующее со снижением функции почек и изменениями морфофункциональных параметров левого желудочка и аорты, свидетельствуют об их значительной роли в процессах поражения кардиоваскулярной системы при ХБП.
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  • 文章类型: Journal Article
    皮肤衍生的晚期糖基化终产物(sAGEs)与成人心血管(CV)风险和死亡率相关。我们假设心肺健康(CRF),体重指数(BMI)和血管健康与儿童期sAGEs的发生有关.
    在我们的前瞻性队列研究中,对1171名6-8岁儿童进行了sAGEs筛查,BMI,视网膜小动脉直径(CRAE)和脉搏波速度(PWV),使用标准化程序。为了确定CRF,进行了20m穿梭运行。四年后,使用相同的方案对675名儿童的所有参数进行了评估.
    较高的初始CRF水平与较低的sAGEs(β[95CI]-0.02[-0.03至-0.002]au,p=0.022)随访时的水平,尽管它们从基线到随访显示出更大的变化(β[95CI]0.02[0.002至0.03]au,p=0.027)。此外,基线sAGEs较高的个体显示CRAE较窄(β[95%CI]-5.42[-8.76至-2.08]μm,p=0.001),在随访时显示CRAE有更大的变化(β[95%CI]-3.99[-7.03至-0.96]μm,p=0.010)从基线到随访。
    运动和更高的CRF可能有助于减轻儿童时期AGEs的形成,从而降低与AGEs诱导的损伤相关的CV疾病的发展风险。预防策略可能需要在生命早期针对CRF,以改善CV危险因素,并可能在以后的生活中抵消CV疾病的发展。
    UNASSIGNED: Skin-derived advanced glycation end products (sAGEs) have been associated with cardiovascular (CV) risk and mortality in adults. We hypothesize that cardiorespiratory fitness (CRF), body mass index (BMI) and vascular health are associated with development of sAGEs during childhood.
    UNASSIGNED: In our prospective cohort study, 1171 children aged 6-8 years were screened for sAGEs, BMI, retinal arteriolar diameters (CRAE) and pulse wave velocity (PWV), using standardized procedures. To determine CRF a 20 m shuttle run was performed. After four 4 years, all parameters were assessed in 675 children using the same protocols.
    UNASSIGNED: Higher initial CRF levels were significantly associated with lower sAGEs (β [95 CI] -0.02 [-0.03 to -0.002] au, p = 0.022) levels at follow-up, although they showed a greater change from baseline to follow-up (β [95 CI] 0.02 [0.002 to 0.03] au, p = 0.027). Moreover, individuals with higher sAGEs at baseline showed narrower CRAE (β [95% CI] -5.42 [-8.76 to -2.08] μm, p = 0.001) at follow-up and showed a greater change in CRAE (β [95% CI] -3.99 [-7.03 to -0.96] μm, p = 0.010) from baseline to follow-up.
    UNASSIGNED: Exercise and higher CRF may help mitigate the formation of AGEs during childhood, thereby reducing the risk for development of CV disease associated with AGEs-induced damage. Preventive strategies may need to target CRF early in life to achieve improvement of CV risk factors and may counteract the development of CV disease later in life.
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  • 文章类型: Journal Article
    精索静脉曲张的热应激可以增加睾丸的氧化应激,影响精子功能和男性生育能力。抗氧化治疗是精索静脉曲张的一种治疗方法,虽然饮食因素像加工食品,糖,饱和脂肪与男性不育有关。晚期糖基化终产物(AGEs),通过糖化过程产生,会引起氧化应激,炎症,和不利的健康后果。α-硫辛酸(ALA),一种多功能的抗氧化剂,可以缓解氧化应激并抵消AGEs的影响,可能通过增强葡萄糖的重吸收。氯化铝(ALT711),抗AGE化合物,通过破坏AGE交联在心血管疾病中表现出希望。这项研究调查了ALA和ALT-711对精索静脉曲张和AGEs动物模型睾丸功能的影响。发现年龄和精索静脉曲张都改变了自然趋势,导致精子参数的异常模式,睾丸功能测试,以及CML的表达,愤怒,和TNF-α蛋白。然而,ALA或ALT711的给药有助于减轻这些影响.虽然与ALT相比,ALA显示出略大的总体益处,差异无统计学意义。
    Heat stress from varicocele can heighten oxidative stress in the testes, impacting sperm function and male fertility. Antioxidant therapy is explored as a remedy for varicocele, while dietary factors like processed foods, sugar, and saturated fats correlate with male infertility. Advanced glycation end products (AGEs), generated through glycation processes, can provoke oxidative stress, inflammation, and adverse health consequences. Alpha-lipoic acid (ALA), a versatile antioxidant, may alleviate oxidative stress and counteract the impact of AGEs, potentially by enhancing glucose reabsorption. Alagebrium chloride (ALT711), an anti-AGE compound, exhibits promise in cardiovascular disease by disrupting AGE cross-links. This study investigates the effects of ALA and ALT-711 on testicular function in varicocele and AGEs animal models. Both AGE and varicocele were found to alter the natural trends, leading to abnormal patterns in sperm parameters, testicular functional tests, as well as the expression of CML, RAGE, and TNF-α proteins. However, the administration of ALA or ALT711 helped mitigate these effects. While ALA demonstrated a slightly greater overall benefit compared to ALT, the difference was not statistically significant.
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  • 文章类型: Journal Article
    晚期糖基化终产物(AGEs)是美拉德反应的最终产物,通过碳水化合物和蛋白质的相互作用形成。反应性二羰基化合物如甲基乙二醛(MGO)用作AGEs形成的前体。在肥胖等疾病中观察到MGO/AGEs水平升高,多囊卵巢综合征(PCOS),糖尿病,对卵母细胞发育产生负面影响。以前的研究表明,硫化氢,具有抗AGEs作用的气体发射器,在受维生素B6影响的过程中产生。R-α-硫辛酸(ALA)抑制蛋白质糖基化和AGEs形成,同时刺激谷胱甘肽(GSH)产生。牛磺酸缓解氧化应激,并作为抗糖基化化合物,防止体外糖基化和AGEs积累。本研究旨在探讨微量营养素支持(牛磺酸,ALA和B6:TAB)对用MGO攻击的小鼠卵母细胞。我们的结果表明MGO降低了卵母细胞的发育能力,虽然TAB补充可以改善成熟,受精,和胚泡形成率。TAB还恢复细胞谱系分配,氧化还原平衡并减轻MGO攻击卵母细胞的线粒体功能障碍。此外,卵丘细胞表达转硫途径的关键酶,和TAB增强它们的mRNA表达。然而,TAB不能挽救MGO诱导的剥脱卵母细胞损伤,强调卵丘细胞的支持作用。总的来说,这些研究结果表明,TAB干预可能对解决与MGO/AGEs水平升高相关的生殖功能障碍具有重要意义.这项研究强调了TAB补充剂在保持暴露于MGO压力的COCs发育能力方面的潜力,为减轻二羰基应激对卵母细胞质量和生殖结果的影响提供见解。
    Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.
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