Role of hepatic cytochromes P450 in bioactivation of the anticancer drug ellipticine: studies with the hepatic NADPH:cytochrome P450 reductase null mouse

Ellipticine is an antineoplastic agent, which forms covalent DNA adducts mediated by cytochromes P450 (CYP) and peroxidases. We evaluated the role of hepatic versus extra-hepatic metabolism of ellipticine, using the HRN (Hepatic Cytochrome P450 Reductase Null) mouse model, in which cytochrome P450 oxidoreductase (POR) is deleted in hepatocytes, resulting in the loss of essentially all hepatic CYP function. HRN and wild-type (WT) mice were treated i.p. with 1 and 10 mg/kg body weight of ellipticine. Multiple ellipticine-DNA adducts detected by (32)P-postlabelling were observed in organs from both mouse strains. Highest total DNA binding levels were found in liver, followed by lung, kidney, urinary bladder, colon and spleen. Ellipticine-DNA adduct levels in the liver of HRN mice were up to 65% lower relative to WT mice, confirming the importance of CYP enzymes for the activation of ellipticine in livers, recently shown in vitro with human and rat hepatic microsomes. When hepatic microsomes of both mouse strains were incubated with ellipticine, ellipticine-DNA adduct levels with WT microsomes were up to 2.9-fold higher than with those from HRN mice. The ratios of ellipticine-DNA adducts in extra-hepatic organs between HRN and WT mice of up to 4.7 suggest that these organs can activate ellipticine and that more ellipticine is available in the circulation. These results and the DNA adduct patterns found in vitro and in vivo demonstrate that both CYP1A or 3A and peroxidases participate in activation of ellipticine to reactive species forming DNA adducts in the mouse model used in this study.     

Ameliorating effects of Nigella sativa oil on aggravation of inflammation,oxidative stress and cytotoxicity induced by smokeless tobacco extract in an allergic asthma model in Wistar rats

Background

The comparison of smokeless tobacco (ST) exposure versus Ovalbumin (Ova) sensitized rats or asthmatic patients has hardly been studied in the literature. Thus, the present study aims to investigate the aggravation of inflammation, exacerbation of asthma, oxidative stress and cytotoxicity induced by ST.

乙脑患儿血清及脑脊液中LPO含量的变化与临床的关系

目的　分析过氧化脂质 ( lipid peroxides,LPO)含量与乙脑患儿脑损伤程度的关系。方法　应用硫代巴比妥酸比色分析法检测 LPO含量。结果　乙脑患儿血清及脑脊液中 LPO含量在初期即有增高 ,极期达高峰 ,恢复期下降。比较各型乙脑患儿血清 LPO含量提示初期与极期差异有显著性 ( P<0 .0 1 ) ,恢复期差异有显著性( P<0 .0 5 ) ;脑脊液 LPO含量在初期与极期差异有显著性 ( P<0 .0 5 ) ,恢复期差异无显著性 ( P>0 .0 5 )。结论LPO参与了乙脑发病过程 ;LPO含量的测定对病情严重程度的判断有重要参考价值     

电子自旋共振和脂质过氧化对亚硒酸钠诱发大鼠白内障的自由基作用研究

以 Ｎａ２ Ｓｅ Ｏ３ 诱发大鼠白内障，用 Ｅ Ｓ Ｒ 波谱仪测到了自由基信号（ｇ＝ ２．００２６），发现注射 Ｎａ２ Ｓｅ Ｏ３后晶体自由基浓度显著高于正常水平，而白内障后期低于晶体正常水平。结果提示，在晶体氧化损伤初期给予抗氧化剂，对白内障的形成有预防和对抗作用，但是在白内障晚期则可能会促进白内障的发展。     

益肾化阏法对Ⅱ型糖尿病血液流变学、SOD、LPO水平及血管病变的影响

目的：观察益肾化瘀法治疗Ⅱ型糖尿病对血液流变学、SOD、LPO水平的影响，并探讨其与血管病变关系。方法Ⅱ型糖尿病符合肾虚血阏证者65例，分为血管病变组和无血管病变组，分别观察治疗前后PBG、PBG、ηb、ηp、IR、SOD、LPO变.2一治疗前血糖、血液流变学、SOD、LPO值具有差异，P＜0．05－0．01。治疗后PBG、PBG、ηb、ηp、IR、SOD、LPO2组均有改善，血液流变学以血管病变组改善明显，血管组FBG与ηb、ηp、IR、LPO呈明显正相关（P＜0．05－0．01），与SOP呈负相关（P＜0．05）。结论益肾化瘀法对Ⅱ型糖尿病及其血管病变具有有效的防治作用。