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《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
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《Saudi Pharmaceutical Journal》2022,30(11):1665-1671
5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p < 0.01). Lycopene alone and combination with 5FU-induced expression of IL-1β, TNF-α, and IL-6. Furthermore, IFN-γ expression was significantly enhanced by only mixture of lycopene (90 µg/ml) and 5FU (p < 0.05). In conclusion, Lycopene supplementation with 5FU therapy resulted in improvement in antioxidant parameters such as catalase and GSH levels giving the cell capacity to cope with 5FU-mediated oxidative stress. Lycopene also enhanced IFN-γ expression in the presence of 5FU, which may activate antitumor effects further enhancing the cancer killing effect of 5FU. 相似文献
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K. Nishiyama S. Murayama Y. Nishimura K. Asayama I. Kanazawa 《Acta neuropathologica》1996,93(1):19-23
Iron accumulation in the basal ganglia and spheroid formation are pathological hallmarks of Hallervorden-Spatz disease (HS).
Since an overaccumulation of iron (iron thesaurosis) that exceeds the binding capacity of ferritin could cause oxidative damage,
we studied the possible role of oxidative stress in the pathogenesis of HS. The basal ganglia and spinal cord from patients
with HS were investigated at autopsy, using histochemistry for iron and immunohistochemistry for Cu/Zn superoxide dismutase
(SOD1), Mn superoxide dismutase (SOD2) and ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred frequently
in spheroids observed in the basal ganglia, and associated iron accumulation indicated the possible existence of increased
oxidative stress in HS patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS, in sharp contrast
with the occasional weak SOD1-IR and SOD2-IR observed in spheroids from patients with amyotrophic lateral sclerosis (ALS).
Neither increased ferritin-IR nor iron accumulation were observed in spinal spheroids from HS and ALS patients. These data
may suggest that, at least in the spinal cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from oxidative
stress directly related to iron accumulation.
Received: 15 March 1996 / Revised accepted: 15 July 1996 相似文献
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本文对17例肾病综合征(NS)患儿和15例健康对照组儿童血红细胞磷脂过氧化氢谷胱甘肽过氧化物酶(PHGPx)活力,脂溶性荧光色素(LSFP)含量进行了研究。结果表明,NS急性期PHGPx活力明显降低.LSFP含量增加;恢复期PHGPx活力较急性期明显提高,但仍低于正常对照组,LSFP虽较急性期下降,但仍高于正常对照组。说明NS存在PHGPx和LSFP的改变,但可逐渐恢复。 相似文献
7.
二十四员大环双核铜(Ⅱ)配合物的合成及其对超氧化物歧化酶的模拟--Ⅱ配合物的歧化超氧离子的活性 总被引:3,自引:0,他引:3
用核黄素光照法测定自合成的2,6-二乙酰基吡啶缩3-氧杂戊烷1,5-二胺大环,H20、im^-、N3^-及SCN^-为桥基的双核铜(Ⅱ)配合物的超氧化物歧化酶活性,它们均在10^-5-10^-7mol/L的浓度范围内具有50%以上抑制率。 相似文献
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目的探讨还原型谷胱甘肽(GSH)在预防糖尿病大鼠勃起功能障碍中的作用。方法通过腹腔注射链脲佐菌素65mg/kg建立糖尿病大鼠模型,然后随机分成DM组和DM+GSH组,DM+GSH组每天肌肉注射GSH200mg/kg。10周后观察大鼠勃起功能,并获取海绵体组织检测其谷胱甘肽、一氧化氮合酶(NOS)与丙二醛(MDA)水平,用TUNEL法检测细胞凋亡。结果成功建立糖尿病大鼠模型。与未注射GSH的DM组相比,DM+GSH组和正常对照组(C组)勃起功能更好,勃起率分别是20%,62.5%和100%。GSH水平DM+GSH组和C组明显比DM组高,其3组含量每克蛋白分别是(75.83±15.62)、(61.47±8.65)和(35.03±12.29)mg(P<0.05);NOS水平在DM+GSH组每毫克蛋白为(133.9±31.9)U,与正常对照组每毫克蛋白为(142.2±31.2)U相当,但较DM组每毫克蛋白为(58.4±18.9)U高(P<0.05);MDA含量在DM组每毫克蛋白为(3.71±0.62)nmol,明显高于正常对照组和DM+GSH组(P<0.05),这两组每毫克蛋白为(2.08±0.34)nmol和(2.44±0.28)nmol;细胞凋亡率在DM组、DM+GSH组和C组的分别是(22.6±3.6)%、(10.8±1.7)%和(7.2±2.1)%(P<0.05)。结论还原型谷胱甘肽对糖尿病大鼠阴茎组织有较好的抗氧化作用,能减少细胞凋亡,对延缓糖尿病性ED的发生有一定的作用。 相似文献
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The immunohistochemical localization of manganese (Mn)-superoxide dismutase (Mn-SOD) was studied in the rat basal forebrain using polyclonal antibodies to Mn-SOD. Neurons of the basal forebrain exhibit a high density of Mn-SOD immunoreactivity. Double immunostaining with a monoclonal antibody to choline acetyltransferase demonstrated that both cholinergic and non-cholinergic neurons in the basal forebrain are intensely immunoreactive for Mn-SOD. 相似文献
10.
从自由基生物学角度评价鸡肉质量的实验研究 总被引:2,自引:0,他引:2
本文把外观健康和非健康的活鸡各20只分成两组,宰后测其肝、腿肌中超氧化物歧化酶(SOD)含量和脂质过氧化产物丙二醛(MDA)水平,发现两组中上述指标值差异显著(P<0.050 ;同时对两组实验鸡胴体在宰后4小时做了感官鉴别,也判断出其品质存在差异。提示体内SOD活性和MDA水平可以反映鸡肉质量,比感官鉴别更具敏感性,同时也可以反映宰前鸡的健康状况。 相似文献