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Reproductive toxicity study with a novel deoxyguanosine analogue (Metacavir) in pregnant SD rats
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作者 Qihui Luo Zhengli Chen +4 位作者 Anchun Cheng Mingshu Wang Jing Fang Xi Peng Li Tang 《Frontiers of Medicine》 SCIE CAS CSCD 2015年第1期82-89,共8页
Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and ... Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different (P 〈 0.01, P 〈 0.05). Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group (P 〈 0.05), while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg· d) there is no teratogenic side effects. 展开更多
关键词 deoxyguanosine analogue Metacavir pregnancy maternal toxicity embryo toxicity TERATOGENICITY
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Sulforaphane Protects Astrocytes Against Oxidative Stress and Delayed Death Caused by Oxygen and Glucose Deprivation 被引量:12
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作者 CAMELIA A.DANILOV KRISH CHANDRASEKARAN +3 位作者 JENNIFER RACZ LUCIAN SOANE CAROL ZIELKE AND GARY FISKUM 《神经损伤与功能重建》 2009年第2期114-124,135,共12页
氧化应激是缺血再灌注后星形胶质细胞损伤和死亡的重要分子机制之一,可能成为有效的干预靶点。下述治疗策略可减轻缺血再灌注条件下产生的多种反应性氮氧化合物损伤。这种方法可通过使用化学试剂或适当条件促进转录活化因子NRF2从细胞... 氧化应激是缺血再灌注后星形胶质细胞损伤和死亡的重要分子机制之一,可能成为有效的干预靶点。下述治疗策略可减轻缺血再灌注条件下产生的多种反应性氮氧化合物损伤。这种方法可通过使用化学试剂或适当条件促进转录活化因子NRF2从细胞浆转入细胞核,并与抗氧化基因反应位点结合,来诱导缺血再灌注后损伤细胞的Ⅱ期基因反应。本研究将验证如下假说:NRF2基因表达通路激活剂sulforaphane能对体外无氧无糖环境处理的培养皮质星形胶质细胞起神经保护作用。将皮质星形胶质细胞暴露于无氧无糖环境(OGD)4 h,于干预前48 h或干预后给予5μMsulforaphane(NRF2基因表达通路激活剂)培养48 h,两种培育条件下细胞死亡均明显减少。免疫细胞化学结果表明干预前给予sulforaphane处理,细胞中DNA/RNA氧化标志物8-hydroxy-2-deox-yguanosine的表达在恢复给氧4 h后降低,两种培育条件下胞浆内及胞核内NRF2的免疫反应均增强且NQO1(NRF2转录活化基因产物)的表达和酶活性均增强。本研究提示sulforaphane可通过激活NRF2抗氧化基因表达通路,减少体外缺氧再灌注后星形胶质细胞的死亡。 展开更多
关键词 缺氧再灌注 NRF2 NQ01 氧化应激 8-hydroxy 2 deoxyguanosine
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Fast electron transfer repair of oxidizing OH adduct of dGMP by chlorogenic acid
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作者 马建华 钱素平 +1 位作者 林维真 姚思德 《Science China Chemistry》 SCIE EI CAS 1998年第5期556-560,共5页
Pulse radiolysis of chlorogenic acid (CGA) as well as CGA and 2′\|deoxyguanosine\|5′\|monophosphate (dGMP) has been carried out in aqueous solution using pulse radiolytic technique. From detailed kinetic analyses, t... Pulse radiolysis of chlorogenic acid (CGA) as well as CGA and 2′\|deoxyguanosine\|5′\|monophosphate (dGMP) has been carried out in aqueous solution using pulse radiolytic technique. From detailed kinetic analyses, the kinetic parameters have been obtained. Accordingly, the reaction mechanisms are suggested. Previous studies have indicated that CGA can either scavenge OH radical or repair oxidizing OH radical adduct of dGMP effectively. 展开更多
关键词 pulse RADIOLYSIS chlorogenic acid 2′\|deoxyguanosine\|5′\|monophosphate.
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