• 【罗丹明通过电子显微镜和共聚焦激光扫描显微镜在体外研究的MGH-U1人癌细胞中的123光毒性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Shea CR,Sherwood ME,Flotte TJ,Chen N,Scholz M,Hasan T
    BACKGROUND & AIMS: :Rhodamine 123 (R123) is a permeant, cationic, fluorescent dye that localizes preferentially within mitochondria of living carcinoma cells. MGH-U1 human bladder carcinoma cells incubated in vitro with 10 microM R123 for 30 min and then irradiated at 514.5 nm with an argon ion laser underwent selective, phototoxic injury to mitochondria. Ultrastructurally, treatment with R123 plus irradiation with 10 J/cm2 caused selective, progressive mitochondrial alterations consisting of disruption of cristae, vacuolization, swelling, increasing numbers of ring-shaped and angulated mitochondria at 4 to 8 h after irradiation, and obliteration of many mitochondria at 24 to 48 h. Confocal laser scanning microscopy after treatment with R123 plus irradiation with 10 to 30 J/cm2 demonstrated altered uptake and localization of subsequently administered R123, accompanied by striking mitochondrial fragmentation. Irradiation caused a dose-dependent depletion of extractable R123, due to a photosensitized efflux that began immediately and progressed by 4 h after irradiation with 10 to 30 J/cm2; further uptake after reincubation in the presence of R123 was also quantitatively impaired in cells previously irradiated with 30 J/cm2.
    背景与目标: 罗丹明123 (R123) 是一种渗透的阳离子荧光染料,优先定位在活癌细胞的线粒体内。MGH-U1人膀胱癌细胞与10 microM R123体外孵育30分钟,然后用氩离子激光在514.5 nm照射,对线粒体进行选择性的光毒性损伤。在超微结构上,用R123加10 J/cm2辐照处理会导致选择性的进行性线粒体改变,包括cr破坏,空泡化,肿胀,照射后4至8小时环形和成角度的线粒体数量增加,以及在24至48小时内许多线粒体消失。用R123加10至30 J/cm2辐照处理后的共聚焦激光扫描显微镜显示,随后施用的R123的摄取和定位发生了改变,并伴有明显的线粒体断裂。辐照导致可提取的R123的剂量依赖性耗竭,这是由于光敏外排立即开始并在用10至30 J/cm2辐照后4小时内进展; 在先前用30 J/cm2辐照的细胞中,在R123存在下重新吸收后的进一步吸收也受到定量损害。
  • 【H1抗组胺药局部用药依米斯汀,依比斯汀和酮替芬的光降解和ROS测试,以评估其有效的光毒性。】 复制标题 收藏 收藏
    DOI:10.3390/pharmaceutics12060560 复制DOI
    作者列表:Gumieniczek A,Berecka-Rycerz A,Hubicka U,Żmudzki P,Lejwoda K,Kozyra P
    BACKGROUND & AIMS: :In this study, important H1 antihistaminic drugs, i.e., emedastine (EME), epinastine (EPI), and ketotifen (KET), were irradiated with UV/Vis light (300-800 nm) in solutions of different pH values. Next, they were analyzed by new high performance liquid chromatography (HPLC) methods, in order to estimate the percentage of degradation and respective kinetics. Subsequently, ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) was used to identify their photodegradation products and to propose degradation pathways. In addition, the peroxidation of linoleic acid and generation of singlet oxygen (SO) and superoxide anion (SA) were examined, together with the molar extinction coefficient (MEC) evaluation, to estimate their phototoxic risk. The photodegradation of all EME, EPI, and KET followed pseudo first-order kinetics. At pH values of 7.0 and 10.0, EPI was shown to be rather stable. However, its photostability was lower at pH 3.0. EME was shown to be photolabile in the whole range of pH values. In turn, KET was shown to be moderately labile at pH 3.0 and 7.0. However, it degraded completely in the buffer of pH 10.0. As a result, several photodegradation products were separated and identified using the UPLC-MS/MS method. Finally, our ROS assays showed a potent phototoxic risk in the following drug order: EPI < EME < KET. All of these results may be helpful for manufacturing, storing, and applying these substantial drugs, especially in their ocular formulations.
    背景与目标: : 在这项研究中,在不同ph值的溶液中用UV/Vis光 (300-800 nm) 照射重要的H1抗组胺药物,即伊美斯汀 (EME) 、依平斯汀 (EPI) 和酮替芬 (KET)。接下来,通过新的高效液相色谱 (HPLC) 方法对它们进行分析,以估计降解百分比和相应的动力学。随后,使用超高效液相色谱串联质谱 (uplc-ms/MS) 鉴定其光降解产物并提出降解途径。此外,还检查了亚油酸的过氧化作用以及单线态氧 (SO) 和超氧阴离子 (SA) 的产生以及摩尔消光系数 (MEC) 的评估,以评估其光毒性风险。所有EME,EPI和KET的光降解均遵循伪一级动力学。在7.0和10.0的ph值下,EPI显示为相当稳定。然而,其在pH 3.0下的光稳定性较低。EME在整个ph值范围内均显示为光不稳定。反过来,KET显示在pH 3.0和7.0下适度不稳定。然而,它在pH 10.0的缓冲液中完全降解。结果,使用uplc-ms/MS方法分离并鉴定了几种光降解产物。最后,我们的ROS测定法按以下药物顺序显示出有效的光毒性风险: EPI < EME
  • 3 Mechanisms of quinolone phototoxicity. 复制标题 收藏 收藏

    【喹诺酮的光毒性机制。】 复制标题 收藏 收藏
    DOI:10.1016/s0378-4274(98)00234-3 复制DOI
    作者列表:Shimoda K
    BACKGROUND & AIMS: :We examined the mechanisms of quinolone phototoxicity in vivo and in vitro. Simultaneous p.o. administration of a quinolone and ultraviolet-A (UVA) irradiation for 4 h induced auricular skin inflammation in BALB/c mice, including edema and neutrophil infiltration in the dermis. Antioxidants inhibited the inflammation in the early stage and cyclooxygenase inhibitors did in both the early and later stages, whereas 5-lipoxygenase inhibitors or histamine antagonists had no effect. The phototoxic inflammation was also induced in mast cell-deficient WBB6F1-W/Wv mice. Corresponding to the in vivo results, incubation with a quinolone under UVA irradiation stimulated BALB/c 3T3 mouse fibroblast cells to release prostaglandin E2 (PGE2) and 6-keto-PGF1alpha, but not leukotriene B4. In contrast, UVA-pre-irradiated quinolones did not affect PG release from fibroblasts. The PGE2 release was inhibited by cyclooxygenase inhibitors, antioxidants, protein kinase C (PKC) inhibitors and a tyrosine kinase (TK) inhibitor, but not by antibodies against tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1). These results lead to a hypothesis that reactive oxygen species generated from quinolones under UVA irradiation trigger PG release from dermal fibroblasts via PKC and TK activation, resulting in skin inflammation and that 5-lipoxygenase products, histamine, TNF alpha or IL-1 is ruled out from the mechanism.
    背景与目标: : 我们在体内和体外研究了喹诺酮的光毒性机制。同时p.o.给予喹诺酮和紫外线-a (UVA) 照射4小时会引起BALB/c小鼠的耳廓皮肤炎症,包括真皮中的水肿和中性粒细胞浸润。抗氧化剂在早期抑制炎症,在早期和晚期均抑制环氧合酶抑制剂,而5-脂氧合酶抑制剂或组胺拮抗剂则无效。在肥大细胞缺陷型WBB6F1-W/Wv小鼠中也诱导了光毒性炎症。与体内结果相对应,在UVA照射下与喹诺酮孵育刺激BALB/c 3T3小鼠成纤维细胞释放前列腺素E2 (PGE2) 和6-keto-pgf1α,但不释放白三烯b4。相反,UVA预辐照的喹诺酮类药物不会影响成纤维细胞中PG的释放。环氧合酶抑制剂,抗氧化剂,蛋白激酶C (PKC) 抑制剂和酪氨酸激酶 (TK) 抑制剂抑制了PGE2的释放,但不受针对肿瘤坏死因子 α (TNF α) 和interleukin-1 (IL-1) 的抗体的抑制。这些结果导致了一个假设,即在UVA照射下由喹诺酮类产生的活性氧物质通过PKC和TK激活触发真皮成纤维细胞释放PG,导致皮肤炎症,并且排除了5-脂氧合酶产物、组胺、TNF-α 或IL-1。
  • 【核黄素浸渍时间的减少不会增加角膜交联过程中内皮细胞光毒性的风险。】 复制标题 收藏 收藏
    DOI:10.1167/tvst.9.6.4 复制DOI
    作者列表:Marcovich AL,Brekelmans J,Brandis A,Samish I,Pinkas I,Preise D,Sasson K,Feine I,Goz A,Dickman MM,Nuijts RMMA,Scherz A
    BACKGROUND & AIMS: Purpose:To evaluate the riboflavin (RF) concentration and distribution in the corneal stroma and the risk for endothelial photodamage during corneal crosslinking (CXL) following 10- and 30-minute impregnation. Methods:De-epithelialized rabbit corneas were subjected to impregnation for 10 and 30 minutes with different RF formulations. Human corneal endothelial cells (HCECs) were subjected to different RF concentrations and ultraviolet A (UVA) dosages. Assays included fluorescence imaging, absorption spectroscopy of corneal buttons and anterior chamber humor, and cell viability staining. Results:After 10 and 30 minutes of impregnation, respectively, anterior chamber fluid showed an RF concentration of (1.6 ± 0.21)•10-4% and (5.4 ± 0.21)•10-4%, and trans-corneal absorption reported an average corneal RF concentration of 0.0266% and 0.0345%. This results in a decrease in endothelial RF concentration from 0.019% to 0.0056%, whereas endothelial UVA irradiance increases by 1.3-fold when changing from 30 to 10 minutes of impregnation. HCEC viability in cultures exposed to UVA illumination and RF concentrations as concluded for the endothelium after 10- and 30-minute impregnation was nonstatistically different at 51.0% ± 3.9 and 41.3 ± 5.0%, respectively. Conclusions:The risk for endothelial damage in CXL by RF/UVA treatment does not increase by shortened impregnation because the 30% increase in light intensity is accompanied by a 3.4-fold decrease of the RF concentration in the posterior stroma. This is substantiated by similar endothelial cell toxicity seen in vitro, which in fact appears to favor 10-minute impregnation. Translational Relevance:This study offers compelling arguments for (safely) shortening RF impregnation duration, reducing patients' burden and costly operation room time.
    背景与目标:
  • 【表面修饰的亚微离子油/水载体包裹的间位四 (羟基苯基) 氯在HT29肿瘤细胞中的细胞摄取,定位和光毒性的比较研究。】 复制标题 收藏 收藏
    DOI:10.1016/s1011-1344(00)00043-9 复制DOI
    作者列表:Bourdon O,Mosqueira V,Legrand P,Blais J
    BACKGROUND & AIMS: :The poor selectivity of photosensitizers for tumor tissue remains a drawback in photodynamic therapy (PDT) and could be improved by adapted formulations. The cellular uptake, localization and phototoxicity of meta-tetra(hydroxyphenyl)chlorin (mTHPC) encapsulated in submicronic colloidal carriers have been studied in macrophage-like J774 cells and HT 29 human adenocarcinoma cells. Nanocapsules with an external layer made of poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG NCs), PLA coated with poloxamer 188 (polox PLA NCs) and oil/water nanoemulsion (NE) have been examined. The cellular uptake by J774, as determined by microspectroflorimetry, is reduced with mTHPC encapsulated into surface-modified NCs--PLA-PEG and polox PLA--compared with naked PLA, indicating a possible limitation of the clearance of such carriers by the reticuloendothelial system. Encapsulation also modifies the interaction between mTHPC and HT29 cells. Compared with the manufacturer's solution (PEG, ethanol, water), the cellular uptake is strongly reduced. However, the HT29 phototoxicity is much less affected and a protecting effect against plasma proteins is observed. Fluorescence microscopy reveals a specific punctate fluorescence pattern with PLA-PEG and polox PLA NCs in contrast to a more diffuse distribution with NE and solution, indicating that photodamage targeting could be different. These findings suggest that photosensitizers encapsulated into surface-modified nanocapsules could be a promising approach for improving PDT efficacy and this has to be confirmed in vivo.
    背景与目标: : 光敏剂对肿瘤组织的选择性差仍然是光动力疗法 (PDT) 的缺点,并且可以通过调整配方来改善。已在巨噬细胞样J774细胞和HT 29人腺癌细胞中研究了封装在亚微离子胶体载体中的间四 (羟基苯基) 氯蛋白 (mTHPC) 的细胞摄取,定位和光毒性。已经检查了具有由聚 (D,L乳酸) (PLA NCs) 制成的外层的纳米胶囊,接枝聚乙二醇的PLA (PLA-PEG NCs),涂有泊洛沙姆188的PLA (polox PLA NCs) 和油/水纳米乳液 (NE)。与裸露的PLA相比,通过显微分光光度法测定的J774的细胞摄取被封装在表面修饰的NCs (PLA-PEG和polox PLA) 中的mTHPC降低,这表明网状内皮系统可能限制了此类载体的清除。封装也改变了mTHPC和HT29细胞之间的相互作用。与制造商的溶液 (PEG,乙醇,水) 相比,细胞摄取大大减少。然而,HT29光毒性的影响要小得多,并且观察到对血浆蛋白的保护作用。荧光显微镜显示出PLA-PEG和polox PLA NCs具有特定的点状荧光模式,而NE和溶液具有更漫射的分布,表明光损伤靶向可能有所不同。这些发现表明,封装在表面改性的纳米胶囊中的光敏剂可能是改善PDT功效的有前途的方法,这必须在体内得到证实。
  • 【茄子提取物在体外和体内模型中保护视网膜色素上皮细胞免受蓝光诱导的光毒性。】 复制标题 收藏 收藏
    DOI:10.3390/nu13020359 复制DOI
    作者列表:Pham TNM,Shin CY,Park SH,Lee TH,Ryu HY,Kim SB,Auh K,Jeong KW
    BACKGROUND & AIMS: :N-retinylidene-N-retinylethanolamine (A2E) accumulation in the retina is a prominent marker of retinal degenerative diseases. Blue light exposure is considered as an important factor contributing to dry age-related macular degeneration (AMD). Eggplant and its constituents have been shown to confer health benefits, but their therapeutic effects on dry AMD remain incompletely understood. In this study, we showed that an extract of Solanum melongena L. (EPX) protected A2E-laden ARPE-19 cells against blue light-induced cell death via attenuating reactive oxygen species. Transcriptomic analysis demonstrated that blue light modulated the expression of genes associated with stress response, inflammation, and cell death, and EPX suppressed the inflammatory pathway induced by blue light in A2E-laden ARPE-19 cells by inhibiting the nuclear translocation of nuclear factor kappa B and transcription of pro-inflammatory genes (CXCL8 and IL1B). The degradation of intracellular A2E was considered the major mechanism underlying the protective effect of EPX. Moreover, chlorogenic acid isolated from EPX exerted protective effects against blue light-induced cell damage in A2E-laden ARPE-19 cells. In vivo, EPX administration in BALB/c mice reduced the fundus damage and degeneration of the retinal layer in a blue light-induced retinal damage model. Collectively, our findings suggest the potential role of Solanum melongena L. extract for AMD treatment.
    背景与目标: : 视网膜中N-亚黄基-N-视黄醇胺 (A2E) 的积累是视网膜退行性疾病的重要标志。蓝光暴露被认为是导致干性年龄相关性黄斑变性 (AMD) 的重要因素。茄子及其成分已被证明具有健康益处,但它们对干性AMD的治疗作用仍未完全了解。在这项研究中,我们证明了茄子的提取物。(EPX) 通过减弱活性氧来保护A2E-laden ARPE-19细胞免受蓝光诱导的细胞死亡。转录组分析表明,蓝光调节与应激反应、炎症和细胞死亡相关的基因的表达,EPX通过抑制核因子 κ B的核易位和促炎基因 (CXCL8和IL1B) 的转录来抑制A2E-laden ARPE-19细胞中由蓝光诱导的炎症途径。细胞内A2E的降解被认为是EPX保护作用的主要机制。此外,从EPX中分离出的绿原酸对A2E-laden ARPE-19细胞中的蓝光诱导的细胞损伤具有保护作用。在体内,在蓝光诱导的视网膜损伤模型中,在BALB/c小鼠中施用EPX可减少眼底损伤和视网膜层变性。总的来说,我们的发现表明茄属提取物在AMD治疗中的潜在作用。
  • 【沥青焦油的光毒性-3T3 NRU PT,3D皮肤模型和实验人体数据的结果之间的对应关系。】 复制标题 收藏 收藏
    DOI:10.1016/j.tiv.2005.06.013 复制DOI
    作者列表:Jirová D,Kejlová K,Bendová H,Ditrichová D,Mezulániková M
    BACKGROUND & AIMS: :Bituminous tars (Ichthammol and Ichthyol Pale) are widely used in pharmaceutical, veterinary and cosmetic industries for their anti-microbial, anti-inflammatory and anti-pruritic effects. In contrast to coal tar, no phototoxicity of bituminous tars has been reported in man, although both Ichthammol and Ichthyol Pale exhibit UV absorption which is higher and broader for the former. The validated 3T3 NRU phototoxicity test indicated phototoxic potential of both substances. The phototoxicity test in a 3D human skin model (EpiDerm) only confirmed phototoxicity for Ichthammol. Human data on Ichthammol phototoxicity are missing. A photopatch test in human volunteers was performed in order to clarify the discrepancy between the phototoxicity found in the skin model and the absence of reported human phototoxicity. Following 4h exposure to 5% and 10% aqueous solutions of Ichthammol and Ichthyol Pale the test sites were irradiated with a UVA dose of 5 J/cm(2). Early phototoxic reaction (erythema) within 4-6h after irradiation was only elicited by Ichthammol and not by Ichthyol Pale. These data correspond well with those from the 3D skin model test and suggest the necessity to employ several test systems for final phototoxicity assessment. In addition to the results obtained in 3T3 NRU PT, further testing on 3D skin models may better reflect bioavailability of a given chemical in the skin, relevant to the situation in humans.
    背景与目标: : 沥青焦油 (鱼腥味和鱼腥味) 因其抗微生物,抗炎和止痒作用而广泛用于制药,兽医和化妆品行业。与煤焦油相反,尽管鱼炭和鱼炭都表现出紫外线吸收,但在人类中没有沥青焦油的光毒性,前者的紫外线吸收更高,更宽。经过验证的3T3 NRU光毒性测试表明两种物质的光毒性潜力。3D人类皮肤模型 (表皮) 中的光毒性测试仅证实了鱼酰胺的光毒性。关于鱼腥草素光毒性的人类数据缺失。为了澄清在皮肤模型中发现的光毒性与没有报告的人类光毒性之间的差异,对人类志愿者进行了光测试。暴露于5% 和10% 的鱼腥酚和鱼腥酚水溶液中4小时后,用5 j/cm(2) 的UVA剂量照射测试部位。辐照后4-6小时内的早期光毒性反应 (红斑) 仅由鱼胺酚引起,而不是由鱼鳞苍白引起。这些数据与3D皮肤模型测试中的数据非常吻合,并建议有必要使用几种测试系统进行最终的光毒性评估。除了在3T3 NRU PT中获得的结果外,在3D皮肤模型上进行的进一步测试可能会更好地反映皮肤中给定化学物质的生物利用度,与人类的情况有关。
  • 【甲氧沙林在各种媒介物中的光毒性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0536.1976.tb03046.x 复制DOI
    作者列表:Suhonen R
    BACKGROUND & AIMS: :Methoxsalen (8-methoxypsoralen) was used as the photoxic substance in the study of the properties of various vehicles in photoepicutaneous testing. Macrogols as such were relatively poor bases, and positive reactions were seen only occasionally at a concentration of 0.05% methoxsalen. Increasing amounts of water in macrogols brought forth more numerous and stronger reactions. The photoxicity also increased when ethanol was added. The reactions were, however, weaker than to those with aqueous bases. Wool fat and glycerol as vehicles usually reacted in the same way as polyethylene glycols when water was added. An explanation of the mechanism of the changes in the properties of vehicles due to the addition of water/ethanol requires further investigation.
    背景与目标: : 甲氧沙林 (8-甲氧基补骨脂素) 被用作光氧化物质,用于研究光表皮测试中各种媒介物的特性。像这样的大分子是相对较差的碱基,并且仅在0.05% 甲氧沙林浓度下偶尔看到阳性反应。大分子中的水量增加会引起更多更强烈的反应。加入乙醇后,光x度也会增加。但是,该反应比具有水性碱的反应弱。当加入水时,作为载体的羊毛脂肪和甘油通常以与聚乙二醇相同的方式反应。对由于添加水/乙醇而导致车辆性能变化的机理的解释需要进一步研究。
  • 【胃癌的癌症新血管靶向近红外光免疫疗法 (NIR-PIT): 与细胞膜靶向的NIR-PIT相比,光毒性的不同机制。】 复制标题 收藏 收藏
    DOI:10.1007/s10120-019-00988-y 复制DOI
    作者列表:Nishimura T,Mitsunaga M,Ito K,Kobayashi H,Saruta M
    BACKGROUND & AIMS: BACKGROUND:Near-infrared photoimmunotherapy (NIR-PIT) constitutes a new class of molecular-targeted theranostics utilizing monoclonal antibody (mAb)-photosensitizer conjugates and NIR light. In this study, we developed a new type of NIR-PIT targeting vascular endothelial growth factor receptor 2 (VEGFR-2) expressed on vascular endothelium in an experimental gastric cancer model and evaluated the feasibility by comparing conventional NIR-PIT targeting cancer cell membrane in vitro and in vivo. METHODS:HER2-positive human gastric cancer cells, NCI-N87, were used for the experiments. Anti-HER2 mAb, trastuzumab and anti-VEGFR-2 mAb, DC101 were conjugated to photosensitizer, IR700. Phototoxicity in response to NIR-PIT were investigated in vitro and in vivo. Microvessel densities, as an indicator of angiogenesis, were counted in harvested xenografts after NIR-PIT to elucidate the mechanism. RESULTS:DC101-IR700 did not induce phototoxic effect in vitro because of the absence of expression of VEGFR-2 in NCI-N87 cancer cells. However, it induced an antitumor effect in NCI-N87 xenograft tumors accompanied with damage in tumor neovasculature as determined by decreasing tumor microvessel density, which represents a different mechanism than that of conventional NIR-PIT targeting antigens expressed on the tumor cell membrane. CONCLUSION:We demonstrated a new approach of NIR-PIT utilizing a target on vascular endothelium, such as VEGFR-2, and this treatment might lead to the development of a new therapeutic strategy for human gastric cancer.
    背景与目标:
  • 【黑色素作为短波长光对视网膜光毒性介体的证据。】 复制标题 收藏 收藏
    DOI:10.1016/0014-4835(92)90069-5 复制DOI
    作者列表:Rapp LM,Smith SC
    BACKGROUND & AIMS: :Albino and pigmented (black-hooded) rats of the Sprague-Dawley and Long Evans strains, respectively, were compared in terms of their susceptibility to retinal damage by ultraviolet-A light. Anesthetized animals were exposed to ultraviolet-A light (lambda max = 360 nm) for 4 hr and retinal damage was assessed 1 week later by electroretinographic analysis and measurement of outer nuclear layer thickness. Albino and pigmented animals showed approximately the same severity of ultraviolet-A retinal damage as a function of exposure irradiance. Furthermore, both pigmentation strains showed swelling and vesiculation of rod inner segment mitochondria as an early manifestation of damage. An abbreviated study on a congenic rat strain (F344-c/+) of albino and pigmented littermates again demonstrated an equal susceptibility to ultraviolet-A phototoxicity for both pigmentation phenotypes. These findings provide evidence that melanin is not the mediator of short-wavelength phototoxicity to the retina, since damage readily occurred in albino animals completely lacking this chromophore.
    背景与目标: : 分别比较了Sprague-Dawley和Long Evans品系的白化病大鼠和有色 (黑帽) 大鼠对紫外线A光对视网膜损伤的敏感性。将麻醉的动物暴露于紫外线A光 (最大 λ = 360 nm) 4小时,并在1周后通过视网膜电图分析和测量外核层厚度评估视网膜损伤。白化病和有色动物表现出与暴露辐照度有关的紫外线-视网膜损伤的严重程度大致相同。此外,两种色素沉着菌株均显示杆状内段线粒体肿胀和囊泡,这是损伤的早期表现。对白化病和有色同窝的同系大鼠品系 (F344-c/) 的简短研究再次表明,两种色素沉着表型对紫外线-a光毒性的敏感性相同。这些发现提供了证据,表明黑色素不是对视网膜短波长光毒性的介体,因为完全缺乏这种发色团的白化病动物很容易发生损害。
  • 【使用不同的光源,方案和大鼠品系的光致视网膜损伤揭示了LED的光毒性。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2016.10.015 复制DOI
    作者列表:Krigel A,Berdugo M,Picard E,Levy-Boukris R,Jaadane I,Jonet L,Dernigoghossian M,Andrieu-Soler C,Torriglia A,Behar-Cohen F
    BACKGROUND & AIMS: :To save energy, the European directives from the Eco-design of Energy Using Products (2005/32/CE) have recommended the replacement of incandescent lamps by more economic devices such as Light Emitting Diodes (LEDs). However, the emission spectrum of these devices is enriched in blue radiations, known to be potentially dangerous to the retina. Recent studies showed that light exposure contributes to the onset of early stages of age-related macular degeneration (AMD). Here, we investigate, in albinos and pigmented rats, the effects of different exposure protocols. Twenty-four hours exposure at high luminance was compared to a cyclic (dark/light) exposure at domestic levels for 1week and 1month, using different LEDs (Cold-white, blue and green), as well as fluorocompact bulbs and fluorescent tubes. The data suggest that the blue component of the white-LED may cause retinal toxicity at occupational domestic illuminance and not only in extreme experimental conditions, as previously reported. It is important to note that the current regulations and standards have been established on the basis of acute light exposure and do not take into account the effects of repeated exposure.
    背景与目标: : 为了节省能源,能源使用产品 (2005/32/CE) 的欧洲指令建议用更经济的设备 (例如发光二极管 (led)) 代替白炽灯。但是,这些设备的发射光谱富含蓝色辐射,已知对视网膜有潜在危险。最近的研究表明,光照会导致年龄相关性黄斑变性 (AMD) 的早期发病。在这里,我们研究了白化病和有色大鼠不同暴露方案的影响。使用不同的led (冷白色,蓝色和绿色) 以及氟紧凑型灯泡和荧光灯管,将高亮度下的24小时曝光与国内水平的循环 (暗/光) 曝光进行了比较。数据表明,如先前报道的那样,白色LED的蓝色成分可能在职业家庭照度下甚至在极端的实验条件下引起视网膜毒性。重要的是要注意,当前的法规和标准是在急性光照的基础上制定的,没有考虑到重复光照的影响。
  • 【用数字投影光刻微图案化的神经培养系统中可见和UVA光毒性的比较。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.a.36540 复制DOI
    作者列表:Khoshakhlagh P,Bowser DA,Brown JQ,Moore MJ
    BACKGROUND & AIMS: :Photopolymerization provides a favorable method for hydrogel formation due to its simplicity, convenience, and versatility. However, the light exposure required to initiate photopolymerization is known to have a cytotoxic effect on encapsulated cells. Here, a 3D in vitro model of the nervous system microenvironment, micropatterned through the use of digital projection photolithography using a single hydrogel formulation that cross-links similarly under ultraviolet A (UVA, 315-400 nm) and visible light (400-700 nm) exposure, is presented. This setup allowed for the investigation of neuronal responses to different light wavelengths and exposure times during photoencapsulation, while ruling out effects due to the hydrogel formulation or photoinitiators used. Cellular studies-including neurite viability, DNA fragmentation, and neurite outgrowth for both UVA and visible light irradiation, the most common spectra used in biological photomicropatterning applications-were performed to assess the effect of light source on neuronal cultures. These studies indicated that while cell death occurs after exposure to either spectrum, visible light was less phototoxic than UVA, when using comparable levels of irradiation, and interestingly, glial cells were more susceptible to phototoxicity than neuronal cells. Thus, while utilizing visible light for micropatterning and cell encapsulation for nervous system applications is beneficial, it is helpful to keep the light exposure low to ensure optimal neuronal survival and growth. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 134-144, 2019.
    背景与目标: : 光聚合由于其简单,方便和多功能性,为水凝胶的形成提供了一种有利的方法。然而,已知启动光聚合所需的光暴露对封装的细胞具有细胞毒性作用。在此,提出了神经系统微环境的3D体外模型,该模型通过使用使用单一水凝胶制剂的数字投影光刻进行微图案化,该单一水凝胶制剂在紫外线a (UVA,315-400 nm) 和可见光 (400-700 nm) 曝光下类似地交联。此设置允许研究光封装过程中神经元对不同光波长和曝光时间的反应,同时排除了由于使用的水凝胶制剂或光引发剂而产生的影响。进行了细胞研究,包括UVA和可见光照射的神经突生存力,DNA片段化和神经突生长,这是生物显微照相法应用中最常用的光谱,以评估光源对神经元培养物的影响。这些研究表明,尽管暴露于任一光谱后都会发生细胞死亡,但当使用相当水平的辐射时,可见光的光毒性比UVA低,有趣的是,神经胶质细胞比神经元细胞更容易受到光毒性。因此,虽然利用可见光进行微图案化和细胞封装用于神经系统应用是有益的,但保持低曝光以确保最佳的神经元存活和生长是有帮助的。©2018威利期刊公司J生物材料Res部分A: 107A: 134-144,2019。
  • 【氧在酞菁光毒性中的作用。】 复制标题 收藏 收藏
    DOI:10.1080/09553009514550111 复制DOI
    作者列表:Rosenthal I,Ben-Hur E
    BACKGROUND & AIMS: :The presence of molecular oxygen is a determinant in the phototoxicity of phthalocyanines, and photosensitized oxidation is the accepted chemical mechanism for photo-dynamic action. However, it is difficult to establish whether the process is initiated by a type I electron transfer, or by a type II energy transfer reaction to form singlet oxygen. Usually, the involvement of singlet oxygen in photodamage has been indicated by the inhibition of the biological effect by a competitive physical or chemical singlet oxygen quencher, or by a rate increase in D2O, in which singlet oxygen has a longer lifetime than in H2O. Unfortunately, these techniques are not completely specific for singlet oxygen. Moreover, thermodynamic considerations suggest that photoinduced electron abstraction from appropriate biomaterials could compete with singlet oxygen production under in vivo conditions. This likely source of one electron-oxidized primary radicals, which can provide the precursors of the oxidative damage in phthalocyanine photosensitization, suggests the possibility of modulated toxicity by interaction with chemical additives. Examples of such additives recently studied are ascorbate, tocopherol and quercetin, all of which are natural antioxidants.
    背景与目标: : 分子氧的存在是酞菁光毒性的决定因素,光敏氧化是公认的光动力作用化学机理。然而,很难确定该过程是由I型电子转移引发的,还是由II型能量转移反应引发以形成单线态氧。通常,单线态氧参与光损伤是通过竞争性物理或化学单线态氧猝灭剂抑制生物效应或D2O速率增加来表明的,其中单线态氧的寿命比H2O更长。不幸的是,这些技术并不完全针对单线态氧。此外,热力学考虑表明,在体内条件下,从适当的生物材料中提取光诱导的电子可以与单线态氧的产生竞争。这种可能的一种电子氧化初级自由基的来源可以提供酞菁光敏化中氧化损伤的前体,这表明通过与化学添加剂的相互作用来调节毒性的可能性。最近研究的此类添加剂的例子是抗坏血酸盐,生育酚和槲皮素,它们都是天然抗氧化剂。
  • 【黄连花序提取物对紫外线B诱导的光毒性的保护作用,并对其化学成分进行hplc-ms分析。】 复制标题 收藏 收藏
    DOI:10.1016/j.fct.2012.04.035 复制DOI
    作者列表:Zhu L,Huang B,Ban X,He J,Chen Y,Han L,Wang Y
    BACKGROUND & AIMS: :Cultivated Coptis chinensis inflorescence has been highly valued in Chinese tea production for many years. The main alkaloid compounds in C. chinensis inflorescence ethanolic extracts (CE) were identified by high-performance liquid chromatography-mass spectrometry. The detected compounds included jatrorrhizine (4.87 mg/g), coptisine (17.18 mg/g), palmatine (3.32 mg/g), and berberine (31.81 mg/g), as well as columbamine and epiberberine (tentatively identified). CE protective activity against ultraviolet-B (UVB)-induced phototoxicity in a mitochondria model was determined by measuring thiobarbituric acid-reactive substrates, lipid hydroperoxide, conjugated diene, 4-hydroxynonenal, and glutathione. The results showed that CE excellently inhibited UVB-induced lipid peroxidation and glutathione reduction in vitro. This photoprotective effect of CE may be caused by the presence of the abovementioned alkaloid compounds and phenolic compounds that enhances CE antioxidant activity. Therefore, CE possesses potent photoprotective property that may find valuable applications in food industries and in anti-phototoxicity formulations.
    背景与目标: : 栽培黄连花序多年来在中国茶叶生产中受到高度重视。通过高效液相色谱-质谱法鉴定了中华长春花花序乙醇提取物 (CE) 中的主要生物碱化合物。检测到的化合物包括药根碱 (4.87 mg/g) 、黄连碱 (17.18 mg/g) 、巴马汀 (3.32 mg/g) 和小檗碱 (31.81 mg/g),以及哥伦巴胺和表小檗碱 (初步鉴定)。通过测量硫代巴比妥酸反应性底物,脂质氢过氧化物,共轭二烯,4-羟基壬烯和谷胱甘肽,确定了对线粒体模型中紫外线B (UVB) 诱导的光毒性的CE保护活性。结果表明,CE在体外对UVB诱导的脂质过氧化和谷胱甘肽还原具有良好的抑制作用。CE的这种光保护作用可能是由于上述生物碱化合物和酚类化合物的存在而引起的,这些化合物可以增强CE的抗氧化活性。因此,CE具有强大的光保护性能,可在食品工业和抗光毒性制剂中找到有价值的应用。
  • 15 Phototoxicity and the cornea. 复制标题 收藏 收藏

    【光毒性和角膜。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Schein OD
    BACKGROUND & AIMS: :The cornea is sensitive to the effects of ultraviolet (UV) light and can suffer both acute and chronic toxicity. Ultraviolet keratitis is associated with relatively short exposures to light sources such as welding arcs or tanning lamps. The corneal effects are seen within a few hours following exposure and typically will resolve within 72 hours. Chronic exposure to environmental UV light may lead to a variety of ocular surface abnormalities that rarely resolve in the absence of therapy. Ultraviolet light, while potentially destructive, also can be used therapeutically. Recently, the photoablative properties of the excimer laser have been used in corneal refractive surgery. This laser uses UV light to break chemical bonds and remove tissue. Corneal phototoxicity is a reflection of the sensitivity of the ocular surface to photochemical injury. Fortunately, effective protection in the form of UV-blocking lenses is widely available.
    背景与目标: : 角膜对紫外线 (UV) 的影响敏感,可遭受急性和慢性毒性。紫外线角膜炎与相对较短的光源暴露有关,例如焊接电弧或晒黑灯。角膜效应在暴露后数小时内可见,通常在72小时内消失。长期暴露于环境紫外线下可能会导致各种眼表异常,这些异常在没有治疗的情况下很少解决。紫外线虽然具有潜在的破坏性,但也可以在治疗上使用。最近,准分子激光的光烧蚀特性已用于角膜屈光手术。这种激光使用紫外线来破坏化学键并去除组织。角膜光毒性是眼表对光化学损伤敏感性的反映。幸运的是,广泛使用防紫外线镜片形式的有效保护。

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