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21.
Pharmaceutical drugs in the wild may pose significant risks to non-target exposed organisms. This situation is even more troublesome for coastal marine or estuarine environments, located in the vicinity of large human conglomerates, for which the putative number of pollutants is extremely high, and the regime by which wild organisms are exposed is continuous. In addition, the number of studies addressing this issue is still scarce, despite evidences that show the potential contamination profiles and adverse biological effects in organisms from such areas. In this study, the ecotoxicity of common pharmaceutical drugs (namely paracetamol and acetylsalicylic acid) was assessed, by studying the susceptibility of the mussel species Mytilus spp to oxidative stress after being exposed for 96 h to increasing but ecologically relevant concentrations of the two mentioned pharmaceuticals (paracetamol: 0, 0.5, 5, 50, and 500 μg/L; acetylsalicylic acid: 0, 0.1, 1, 10, and 100 μg/L). The oxidative status in exposed organisms was analyzed by measuring oxidative stress biomarkers, namely catalase (CAT), glutathione-S-transferases (GSTs), and lipoperoxidation (LPO) levels, whose alteration was indicative of chemical exposure, in both digestive gland and gills of the organisms. In addition, the food uptake and the nutritional reserve status of exposed organisms were also assessed, by measuring the consumption of ingested food, and levels of tissue reserves of glycogen in gills and digestive gland. No significant alterations were observed in the assessed oxidative stress parameters so it was possible to hypothesize that the studied drugs may have probably exerted a limited alteration of antioxidant defenses and damage, which was reverted by the activation of defensive adaptive mechanisms. This set of data evidenced that the pro-oxidative metabolism that was already described for both drugs in other animal models, was not fully established in the exposed mussels. On the contrary, glycogen reserves were substantially changed after exposure to both toxicants, being possible to observe opposite responses caused by both drugs. Food uptake was not altered following exposure to the drugs. Further evaluations are thus required to conclude about both drugs ecotoxicity and other parameters, namely seasonality, which should be considered when performing ecotoxicology tests, especially with the selected species. 相似文献
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中药具有多成分、多靶点的特性,药效物质基础及药物代谢途径不明确严重制约中药的发展。中药小分子经过体内代谢后转化成代谢物发挥药效或者清除。近年来随着MS技术的飞速发展,通过LC-MS技术进行精准定性定量分析,以阐明中药代谢物与机体生理及病理相关变化的关系,从而明确中药的药效物质基础及体内代谢路径。本文从中药代谢研究思路、研究方法、影响因素以及应用等方面,就近年来中药代谢分析领域的研究进展进行综述。 相似文献
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Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d9-methadone.The pharmacokinetic profiles of d9-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d9-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD50 value for a single intravenous dose of d9-methadone was 2.1-fold higher than that for methadone. Moreover, d9-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy. 相似文献
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多囊卵巢综合征(polycystic ovary syndrome,PCOS)是一种常见于育龄妇女的内分泌代谢性疾病,以月经不规则、高雄激素血症和卵巢多囊样改变为特征,常表现为肥胖、不孕和胰岛素抵抗。硫氧还蛋白相互作用蛋白(thioredoxin-interacting protein,TXNIP)是一种多功能调节剂,不仅参与胰岛素分泌和葡萄糖代谢的调节,还与氧化应激、炎症因子和情绪障碍密切相关。PCOS患者体内的TXNIP水平较健康人群明显增加,表明TXNIP可能参与PCOS及其并发症的发生、发展。近年体内外研究尝试应用中药提取物和西医药物抑制TXNIP的表达,TXNIP特异性抑制剂的发现使TXNIP有望成为抑制PCOS进程的有效靶点。综述TXNIP在PCOS中的作用进展,以期为PCOS发病机制的深入研究及临床诊疗提供新的思路和方向。 相似文献
27.
Imaging techniques based on retinal autofluorescence have found broad applications in ophthalmology because they are extremely sensitive and noninvasive. Conventional fundus autofluorescence imaging measures fluorescence intensity of endogenous retinal fluorophores. It mainly derives its signal from lipofuscin at the level of the retinal pigment epithelium. Fundus autofluorescence, however, can not only be characterized by the spatial distribution of the fluorescence intensity or emission spectrum, but also by a characteristic fluorescence lifetime function. The fluorescence lifetime is the average amount of time a fluorophore remains in the excited state following excitation. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is an emerging imaging modality for in vivo measurement of lifetimes of endogenous retinal fluorophores. Recent reports in this field have contributed to our understanding of the pathophysiology of various macular and retinal diseases.Within this review, the basic concept of fluorescence lifetime imaging is provided. It includes technical background information and correlation with in vitro measurements of individual retinal metabolites. In a second part, clinical applications of fluorescence lifetime imaging and fluorescence lifetime features of selected retinal diseases such as Stargardt disease, age-related macular degeneration, choroideremia, central serous chorioretinopathy, macular holes, diabetic retinopathy, and retinal artery occlusion are discussed. Potential areas of use for fluorescence lifetime imaging ophthalmoscopy will be outlined at the end of this review. 相似文献
28.
Camila L.P. Oliveira Stephanie Mattingly Ralf Schirrmacher Michael B. Sawyer Eugene J. Fine Carla M. Prado 《Journal of the Academy of Nutrition and Dietetics》2018,118(4):668-688
The predominant use of glucose anaerobically by cancer cells (Warburg effect) may be the most important characteristic the majority of these cells have in common and, therefore, a potential metabolic pathway to be targeted during cancer treatment. Because this effect relates to fuel oxidation, dietary manipulation has been hypothesized as an important strategy during cancer treatment. As such, the concept of a ketogenic diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism) rather than a dietary approach. The therapeutic mechanisms of action of this high-fat, moderate-to-low protein, and very-low-carbohydrate diet may potentially influence cancer treatment and prognosis. Considering the lack of a dietetics-focused narrative review on this topic, we compiled the evidence related to the use of this diet in humans with diverse cancer types and stages, also focusing on the nutrition and health perspective. The use of KD in cancer shows potentially promising, but inconsistent, results. The limited number of studies and differences in study design and characteristics contribute to overall poor quality evidence, limiting the ability to draw evidence-based conclusions. However, the potential positive influences a KD may have on cancer treatment justify the need for well-designed clinical trials to better elucidate the mechanisms by which this dietary approach affects nutritional status, cancer prognosis, and overall health. The role of registered dietitian nutritionists is demonstrated to be crucial in planning and implementing KD protocols in oncology research settings, while also ensuring patients’ adherence and optimal nutritional status. 相似文献
29.
Sara Matić Milena Jadrijević-Mladar Takač Monika Barbarić Bono Lučić Koraljka Gall Trošelj Višnja Stepanić 《Journal of pharmaceutical sciences》2018,107(11):2957-2964
The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B. 相似文献
30.
Lin Yuan Caijuan Liang Xinpeng Diao Xiaoye Cheng Man Liao 《Xenobiotica; the fate of foreign compounds in biological systems》2018,48(4):332-341
Hydroxygenkwanin (HYGN) and genkwanin (GN) are major constituents of Genkwa Flos for the treatment of edema, ascites, cough, asthma and cancer. This is a report about the investigation of the metabolic fate of HYGN and GN in human liver microsomes and the recombinant UDP-glucuronosyltransferase (UGT) enzymes by using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). An on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was developed to trace all probable metabolites. Based on this analytical strategy, three phase I metabolites and seven glucuronide conjugation metabolites of HYGN, seven phase I metabolites and 12 glucuronide conjugation metabolites of GN were identified in the incubation samples of human liver microsomes. The results indicated that demethylation, hydroxylation and o-glucuronidation were main metabolic pathways of HYGN and GN. The specific UGT enzymes responsible for HYGN and GN glucuronidation metabolites were identified using recombinant UGT enzymes. The results indicated that UGT1A1, UGT1A3, UGT1A9, UGT1A10 and UGT2B7 might play major roles in the glucuronidation reactions. Overall, this study may be useful for the investigation of metabolic mechanism of HYGN and GN, and it can provide reference and evidence for further experiments. 相似文献