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排序方式: 共有87条查询结果,搜索用时 15 毫秒
1.
目的:在先期研究已证实环磷酰胺(Cyclophosphamide,CP)代谢产物丙烯醛(Acrolein,ACR)的氧化应激作用损伤支持细胞是CP所致睾丸损伤的原因之一的基础上探讨具有抗氧化作用的银杏黄酮对其损伤的保护作用.方法:以原代培养的新生Wistar大鼠支持细胞为模型,实验组分为1)添加银杏黄酮孵育细胞12h后加入ACR组;2)银杏黄酮、ACR同时加入组;3)银杏黄酮和ACR孵育12h后再加入细胞组.对照组分为添加维生素E孵育细胞12h后分别加入ACR组,仅添加ACR的阴性对照组及不添加任何处理因素的阳性对照组.各组3h后用MTT法测定细胞活性,考马斯亮蓝法测定蛋白浓度;硫代巴比妥法和Fenton法检测细胞丙二醛(MDA)、羟自由基(OH)含量,三价铁还原法、黄嘌呤氧化酶法和NADPH还原法测定细胞总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性和谷胱甘肽还原酶(GR)活性.结果:银杏黄酮与ACR同时加入细胞组和银杏黄酮与ACR孵育12h后同时加入组较阴性对照组各测量参数无显著性差异(P>0.05).而提前添加银杏黄酮组较阴性对照组各参数均有显著性差异:1)细胞活力较阴性对照组显著升高(P<0.05);2)MDA和T-ACO含量较阴性对照组明显降低(P<0.05);3)T-AOC、SOD和GR活性较阴性对照组明显升高(P<0.05).且银杏黄酮上述抗氧化作用明显强于Vit E组(P<0.05)结论:CP代谢产物ACR在对未成熟睾丸支持细胞产生氧化应激损害时,银杏黄酮可以提高支持细胞的抗氧化酶活性,清除氧自由基,对支持细胞具有明显的保护作用.为进一步探讨CP致睾丸损伤的防护措施奠定了基础. 相似文献
2.
目的 采用蛋白组学方法研究丙烯醛雾化吸入致大鼠慢性支气管肺炎模型中依那普利干预后肺组织蛋白组的表达变化,探讨依那普利干预慢性支气管肺炎的分子机制.方法 运用双向电泳和质谱分析技术找出丙烯醛雾化吸入组和依那普利干预组的差异蛋白质.结果 在两组凝胶图谱中平均检测到545个蛋白点.依那普利干预组与丙烯醛吸入组比较,发现3个明显差异蛋白.经质谱鉴定, 3个差异蛋白分别是甘油醛-3-磷酸脱氢酶,T-激肽原-1-前体,二氢嘧啶酶-2.定量分析结果显示依那普利干预导致肺组织中二氢嘧啶酶-2上调,甘油醛-3-磷酸脱氢酶下调,而T-激肽原-1-前体消失.结论 依那普利对大鼠慢性支气管肺炎的干预作用可能与肺组织中这3种蛋白表达变化有关. 相似文献
3.
目的探讨磷酸二酯酶4(PDE4)抑制剂YM976对慢性阻塞性肺疾病(COPD)大鼠肺粘液分泌的影响。方法将40只SD大鼠随机等分为4组:正常对照组、药物对照组、COPD模型组、药物干预组。测定支气管肺泡灌洗液(BALF)中的细胞总数和巨噬细胞绝对计数及百分比,阿辛蓝和MUC5AC免疫组化染色检测MUC5AC表达,RT-PCR检测MUC5AC mRNA在肺组织中的表达。结果YM976可以降低丙烯醛诱导的COPD大鼠BALF中的细胞总数和肺泡巨噬细胞计数及百分比,降低其肺组织MUC5AC的mRNA水平和MUC5AC蛋白表达。结论YM976能有效减少大鼠BALF中细胞总数和巨噬细胞数,从蛋白和基因水平抑制大鼠肺组织MUC5AC的表达。 相似文献
4.
《Drug metabolism reviews》2012,44(4):651-675
Modification of proteins in conditions of oxidative stress can contribute to protein dysfunction or tissue damage and disease progression. Bifunctional, most often α,β-unsaturated carbonyl compounds such as 4-hydroxy-2-nonenal (HNE), 4-oxo-2-nonenal (ONE), and acrolein, generated from oxidation of polyunsaturated fatty acids (PUFAs), readily bind to protein nucleophiles. Modification by bifunctional aldehydes can also lead to intramolecular or intermolecular protein crosslinking. Model studies are revealing the structure of adducts that can then be more readily identified in mass spectrometric studies on proteins exposed to the various pure aldehydes or to peroxidized PUFAs. Although simple Michael and Schiff base adducts are often formed initially, only some of these adducts, such as the HNE- and ONE-derived Michael adducts on Cys and His residues, are found to survive the conditions of proteolysis and HPLC-MS analysis. Reversibly formed adducts, such as the HNE-Lys Michael adduct, can be found on proteolytic peptides only if a NaBH4-reduction step is used prior to proteolysis. Initial adducts can evolve by tautomerization, oxidation, cyclization, dehydration, and sometimes condensation with a second aldehyde molecule (the same or different), to give stable advanced lipoxidation end products (ALEs) that can be found by mass spectrometry. These include the HNE-Lys-derived 2-pentylpyrrole, the ONE-Lys-derived 4-ketoamide, the ONE-derived His-Lys pyrrole crosslink, and a Lys-derived 3-formyl-4-pentylpyrrole that results from combined action of ONE and acrolein. Michael adducts of α,β-unsaturated aldehydes such as HNE and ONE can be derivatized by 2,4-dinitrophenylhydrazine (DNPH) and can thus constitute significant DNPH-detectable protein-bound carbonyl activity that serves as a key indicator of oxidative stress in tissues. It appears that lipid oxidation is a more important contributor to such activity than metal-catalyzed oxidation of protein side-chains. 相似文献
5.
Timothy E. O'Toole Yu-Ting Zheng Jason Hellmann Daniel J. Conklin Oleg Barski Aruni Bhatnagar 《Toxicology and applied pharmacology》2009,236(2):194-34
Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca2+]i), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca2+]I with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca2+]I, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure. 相似文献
6.
Clelia RamelloPatrick Paullier Aissa Ould-DrisMatthieu Monge Cécile LegallaisEric Leclerc 《Toxicology in vitro》2011,25(5):1123-1131
In this study we present a method for investigating the effect of acrolein, a nephrotoxic and urotoxic metabolite of the anticancerous prodrugs ifosfamide and cyclophosphamide, in a blood-renal barrier biochip. The real time monitoring of mass transfers of caffeine, vitamin B12 and albumin in the biochip was performed thanks to an in vitro dialysis method. The diffusion coefficients of the solutes and their dialysance from the apical to the basolateral compartments were found to be molecular weight and cell-membrane dependent, thus demonstrating the cell-barrier functionality. The toxicity induced by the acrolein led to modifications to mass transfer properties which appeared to be acrolein dose, time and solute molecular weight dependent. Solute mass transfer across the cell layer increased with acrolein concentrations. The sensitivity of this analysis method contributes to identify the mass transfer properties and to monitor the modification to the renal parameter when submitted to toxic cell compounds. The results provide the foundation for exploring kidney behavior in response to drugs thanks to a blood-tissue barrier model using a technique based on in vitro dialysis and real time analysis. 相似文献
7.
Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund’s adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol–induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol– and WS-12–induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects. 相似文献
8.
Cyclophosphamide must be metabolized by drug-oxidating systems in order to become biologically active. Up to now, it is not known exactly which metabolite is responsible for the teratogenic effects of the drug. Besides aldophosphamide and phosphoramide mustard, the metabolite acrolein must be considered as a possible candidate. We tested this unsaturated aldehyde in a mouse limb bud culture system, since results from in vivo studies are controversial and inconclusive.The following results were obtained: (1)Concentrations of acrolein between 3 and 10mg/1 induce a significant impairment of limb bud differentiation with expiants from 12-day-old mouse embryos. Scapula and paw skeleton were more affected than ulna and radius. (2) With limbs from 11-day-old embryos we found similar effects, even at lower concentrations. (3) A contact time of 20–40 min is sufficient to induce abnormal development. (4) It is possible to antagonize the teratogenic effect of acrolein by addition of mesna (300 mg/1) to the culture medium. (5) The abnormalities observed with acrolein under these experimental conditions are clearly different from those seen with hydroperoxy-cyclophosphamide. 相似文献
9.
Background
It has been suggested that nitric oxide (NO) affects the afferent pathways innervating the bladder. In addition, acrolein, a metabolite of cyclophosphamide, causes bladder hypersensitivity in rats.Objective
We investigated the direct effects of an NO substrate (L-arginine) and an NO synthase inhibitor (Nω-nitro-L-arginine methyl ester hydrochloride [L-NAME]) on single fiber activities of the primary bladder afferent nerves with or without acrolein application.Design, setting, and participants
Female Sprague-Dawley rats were used. Under urethane anesthesia, a single nerve fiber primarily originating from the bladder was identified by electrical stimulation of the left pelvic nerve and by bladder distention, and it was divided by conduction velocity as Aδ fiber or C fiber.Measurements
The afferent activity measurements with constant bladder filling were repeated three times, and the third measurement served as the baseline observation. After that, two experiments were performed. First, L-NAME (10 mg/ml) was instilled intravesically. Then L-arginine (300 mg/kg) was administrated intravenously to investigate the competition with L-NAME. Second, L-arginine was administrated intravenously. Then 0.003% of acrolein or saline was instilled intravesically to obtain another three cycles of instillations.Results and limitations
Forty-two single afferent fibers (Aδ fibers: n = 19; C fibers: n = 23) were isolated in 31 rats. When the bladder was filled with L-NAME solution, afferent activities of both Aδ and C fibers increased significantly, and L-arginine administration inhibited these stimulated responses. In addition, intravenous administration of L-arginine significantly decreased the activities of both fibers during saline instillation. Intravesical acrolein instillation significantly increased the activities of both fibers, which were inhibited by pretreatment with L-arginine.Conclusions
The results suggest that NO synthase exists in the rat urinary bladder and clearly demonstrate that L-arginine, an NO substrate, can inhibit both Aδ and C mechanosensitive afferent fibers of the bladder in the rat. In addition, L-arginine can inhibit the activated responses of both fibers to intravesical acrolein. 相似文献10.
The study objective was to determine the effect of variable power applied to the atomizer of refillable tank based e-cigarette (EC) devices. Five different devices were evaluated, each at four power levels. Aerosol yield results are reported for each set of 25 EC puffs, as mass/puff, and normalized for the power applied to the coil, in mass/watt. The range of aerosol produced on a per puff basis ranged from 1.5 to 28 mg, and, normalized for power applied to the coil, ranged from 0.27 to 1.1 mg/watt. Aerosol samples were also analyzed for the production of formaldehyde, acetaldehyde, and acrolein, as DNPH derivatives, at each power level. When reported on mass basis, three of the devices showed an increase in total aldehyde yield with increasing power applied to the coil, while two of the devices showed the opposite trend. The mass of formaldehyde, acetaldehyde, and acrolein produced per gram of total aerosol produced ranged from 0.01 to 7.3 mg/g, 0.006 to 5.8 mg/g, and <0.003 to 0.78 mg/g, respectively. These results were used to estimate daily exposure to formaldehyde, acetaldehyde, and acrolein from EC aerosols from specific devices, and were compared to estimated exposure from consumption of cigarettes, to occupational and workplace limits, and to previously reported results from other researchers. 相似文献