Effects of malachite green on the mRNA expression of detoxification‐related genes in Nile tilapia (Oreochromis niloticus) and other major Chinese freshwater fishes

The use of malachite green (MG) in fish farming is prohibited in China due to its potentially toxicological and carcinogenic nature, but it is still illegally used in some places. The aim of this study was to investigate the time and concentration‐dependent responses of xenobiotic metabolizing and detoxification‐related genes in diverse fishes exposed to MG both in vivo and in vitro. Experimental fish were administered to two exposure groups of malachite green (MG) (0.10 and 0.50 mg L^?1) for 8 h. The hepatocytes isolated from Nile tilapia were incubated with MG (0.5, 1.0, and 2.0 mg L^?1) for 8 and 24 h, respectively. In vivo, exposure to 0.10 and 0.50 mg L^?1 MG for 8 h caused significant changes of the detoxification‐related genes on the mRNA expression levels. Low‐concentration (0.10 mg L^?1) level of MG induced significant increase on the mRNA expression level of GSTR gene in Nile tilapia and other fishes. The mRNA expression of grass carp UCP2 was significantly induced when exposed to 0.5 mg L^?1 MG. However, the mRNA expression levels of GSTA, CYP1A, and GPX were inhibited significantly by 0.5 mg L^?1 MG in Nile tilapia, grass carp, and Taiwan snakehead. In vitro, the significant increase of mRNA expression of these genes was detected after exposure to 0.5 mg L^?1 MG (UCP2), and 1.0 mg L^?1 MG (CYP1A1, GSTA, GSTR, and UCP2). The induction of hepatic CYP1A1, GSTA, GSTR, and UCP2 in response to MG suggested a potential role of fish CYP1A1, GSTA, GSTR, and UCP2 in MG metabolism. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.     

我国短缺药品现状调查分析

目的:为解决我国短缺药品问题提供参考。方法:采用文献调研、问卷调研(10省市共177家医疗机构)与实地考察(3家药品流通企业)方式对我国短缺药品现状进行综合分析。结果与结论:调研得到284种涉及短缺的药品,属于《国家基本药物目录》的198种,属于《国家基本医疗保险和工伤保险药品目录》的222种,属于《社区卫生服务机构用药参考目录》的104种,且几乎覆盖全部治疗领域。分析表明我国药品短缺现象确实存在,但多为综合原因引起的局部短缺,与我国医药卫生领域生产和流通环节"多小散乱"的格局和行业恶性竞争有直接联系。     

复方黄连胶囊降血糖作用的实验研究

目的:研究复方黄连胶囊(CRCC)降血糖作用及部分机制。方法:建立大鼠四氧嘧啶糖尿病模型,观察CRCC对血糖、血清胰岛素、糖化血红蛋白、糖耐量、心肌组织内脂质过氧化水平的影响。结果:CRCC(1．09, 2．18,4．36 g·kg~(-1),ig给药)能降低糖尿病大鼠的血糖和糖化血红蛋白,升高血清胰岛素水平,增强其糖耐量,并能抑制心肌的脂质过氧化反应。结论:CRCC具有降血糖作用,并可通过改善心肌组织内脂质过氧化作用对心肌产生保护作用。     

科罗索酸对大鼠嗜铬细胞瘤PC12细胞缺氧缺糖损伤的保护作用

目的 研究科罗索酸(三萜类降血糖药)对PC12细胞缺氧缺糖损伤的保护作用.方法 用连二亚硫酸钠(Na2S2O4)合并缺糖,致PC12细胞缺氧缺糖损伤模型,用MTT法测定细胞活力;用紫外分光光度法测定细胞上清液乳酸脱氢酶(LDH)释放量、细胞内乳酸(LD)和超微量ATP酶的活力.结果 与模型对照组比较,2个浓度(10,1μmol·L-1)科罗索酸可显著升高细胞活力,降低上清液LDH和细胞内LD含量,增强损伤细胞内Na+一K+ATP酶活力(P<0.05,P<0.01).结论 科罗索酸对PC12细胞缺氧缺糖损伤模型有明显的保护作用.     

Quantitative assessment of the contribution of sodium‐dependent taurocholate co‐transporting polypeptide (NTCP) to the hepatic uptake of rosuvastatin,pitavastatin and fluvastatin

Hepatic uptake transport is often the rate‐determining step in the systemic clearance of drugs. The ability to predict uptake clearance and to determine the contribution of individual transporters to overall hepatic uptake is therefore critical in assessing the potential pharmacokinetic and pharmacodynamic variability associated with drug–drug interactions and pharmacogenetics. The present study revisited the interaction of statin drugs, including pitavastatin, fluvastatin and rosuvastatin, with the sodium‐dependent taurocholate co‐transporting polypeptide (NTCP) using gene transfected cell models. In addition, the uptake clearance and the contribution of NTCP to the overall hepatic uptake were assessed using in vitro hepatocyte models. Then NTCP protein expression was measured by a targeted proteomics transporter quantification method to confirm the presence and stability of NTCP expression in suspended and cultured hepatocyte models. It was concluded that NTCP‐mediated uptake contributed significantly to active hepatic uptake in hepatocyte models for all three statins. However, the contribution of NTCP‐mediated uptake to the overall active hepatic uptake was compound‐dependent and varied from about 24% to 45%. Understanding the contribution of individual transporter proteins to the overall hepatic uptake and its functional variability when other active hepatic uptake pathways are interrupted could improve the current prediction practice used to assess the pharmacokinetic variability due to drug–drug interactions, pharmacogenetics and physiopathological conditions in humans. Copyright © 2013 John Wiley & Sons, Ltd.     

Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus

PM_2.5 travels along the respiratory tract and enters systemic blood circulation. Studies have shown that PM_2.5 increases the incidence of various diseases not only in adults but also in newborn infants. It causes chronic inflammation in pregnant women and retards fetal development. In this study, pregnant rats were exposed to PM_2.5 for extended periods of time and it was found that PM_2.5 exposure increased immune cells in mother rats. In addition, cytokines and free radicals rapidly accumulated in the amniotic fluid and indirectly affected the fetuses. The authors collected cerebral cortex and hippocampus samples at E18 and analyzed changes of miRNA levels. Expression levels of cortical miR‐6315, miR‐3588, and miR‐466b‐5p were upregulated, and positively correlated with the genes Pkn2 (astrocyte migration), Gorab (neuritogenesis), and Mobp (allergic encephalomyelitis). In contrast, PM_2.5 decreased expression of miR‐338‐5p and let‐7e‐5p, both related to mental development. Further, PM_2.5 exposure increased miR‐3560 and let‐7b‐5p in the hippocampus, two proteins that regulate genes Oxct1 and Lin28b that control ketogenesis and glycosylation, and neural cell differentiation, respectively. miR‐99b‐5p, miR‐92b‐5p, and miR‐99a‐5p were decreased, leading to reduced expression of Kbtbd8 and Adam11 which reduced cell mitosis, migration, and differentiation, and inhibited learning abilities and motor coordination of the fetus. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1412–1425, 2017.     

甲磺酸多沙唑嗪片的人体药动学研究

目的研究甲磺酸多沙唑嗪片在中国健康人体内的药动学.方法液相色谱质谱联用法(HPLC-MS)测定12名健康男性受试者单剂量口服4 mg甲磺酸多沙唑嗪片后的血药浓度,由DAS2.0药学与统计程序处理计算药动学参数.结果建立的分析方法在0.5～100μg·L-1范围内线性关系良好(r=0.997 7),平均回收率为98.33%,日内RSD为8.43%,日间RSD为9.5%.12名受试者单次服用4 mg甲磺酸多沙唑嗪片后,体内呈二室模型药动学特征,主要的药动学参数tmax、Cmax、Ka、t1/2β及V/F分别为3.0 h、47.66μg·L-1、0.763,26.19 h和5.40 L.结论分析方法准确、灵敏度高,主要药动学参数与文献报道相似.     

Effects of di(2‐ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium‐deficient and selenium‐supplemented rats

Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3‐weeks‐old Sprague–Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se‐supplementation group was on 1 mg Se/kg diet. DEHP‐treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S‐transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10‐fold) and marked increase in TBARS levels, and its effects were more pronounced in Se‐deficient rats with ～18.5‐fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 98–107, 2014.