N-乙酰半胱氨酸对重型病毒性肝炎患者血清sIcAM-1水平的影响

目的:探讨N-乙酰半胱氨酸(NAC)对重型病毒性肝炎(重肝)患者血清可溶性细胞间粘附分子-1(sIcAM-1)水平的影响,为重肝提供新的治疗方法。方法:采用夹心酶联免疫吸附法(ELISA法)分析65例重肝患者血清sIcAM-1的水平表达,通过NAC治疗组(29例)与综合治疗B组(36例)的自身治疗前、后及治疗后两组疗效的对比,观察NAC治疗30天后sIcAM-1水平表达的变化。结果:重肝患者血清sIcAM-1水平较正常对照组有非常显著性增高。治疗组slcAM-1自身治疗前、后比较有非常显著性意义。NAC治疗前后有效病例slcAM-1水平随病情好转而滴度下降,差异有显著性意义(P<0.001),无效病例sIcAM-1水平随病情恶化而滴度上升(P<0.05);治疗组中有效与无效者治疗后slcAM-1水平分别与综合组中有效与无效病例比较明显下降(P<0.05～0.001)。结论:sIcAM-1水平变化与重肝损伤程度密切相关,可作为判定重肝早期指标之一;NAC可降低sIcAM-1水平,对重肝治疗有效。     

Gastrointestinal metabolism of N-acetylcysteine in the rat, including an assay for sulfite in biological systems

The intestinal metabolism of N-acetylcysteine was studied in the rat. Isolated intestinal epithelial cells were shown to rapidly deacetylate [14C]-N-acetylcysteine to [14C]-cysteine, with slight oxidation of the latter to disulfide species. The cells did not accumulate reduced or oxidized cysteine, and N-acetylcysteine itself was not detected either free or in oxidized species intracellularly. Further metabolism of this NAC-derived cysteine to inorganic sulfite or glutathione was not detected. Following the administration of [14C]-N-acetylcysteine (50 mg/kg; 25 microCi) in vivo into the ilium, small quantities of both reduced and oxidized [14C]-N-acetylcysteine were demonstrated in hepatic portal vein plasma. [14C]-cysteine and inorganic sulfite were demonstrated as the major metabolites of N-acetylcysteine. These were present in the portal vein plasma at levels five and three times greater than the parent drug, respectively, 30 min after dosing. Additionally, [14C]-glutathione was shown to be a minor metabolite of N-acetylcysteine accumulating in portal vein plasma. These results may provide an explanation for the apparent low bioavailability of N-acetylcysteine when administered orally in humans and are discussed in terms of the origins of the protective effect of the drug in cases of paracetamol intoxication in humans.     

N-acetylcystein in dengue associated severe hepatitis

Although, N-acetylcystein (NAC) has shown benefit in non-acetaminophen related liver failure, it was not well studies in dengue associated severe hepatitis. We report a case of dengue hemorrhagic fever associated severe hepatitis (encephalopathy grade 2-drowsy and intermittent disorientation) treated with NAC resulted in good outcome without hepatic transplantation.     

Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells through a ROS-dependent mechanism

CDDO-Me, a synthetic triterpenoid derived from oleanolic acid, is a promising anticancer agent that has shown strong activity against a wide variety of cancer types in vitro and in vivo. We have previously shown that CDDO-Me induces apoptosis in prostate cancer cells irrespective of their hormonal status. To further understand the proapoptotic mechanism of CDDO-Me, we investigated the role of reactive oxygen species (ROS) in mediating the apoptosis inducing activity of CDDO-Me in LNCaP and PC-3 prostate cancer cell lines. Here, we show that CDDO-Me induces ROS generation from both nonmitochondrial and mitochondrial sources, which is associated with the induction of apoptosis as characterized by increased annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c. In addition, CDDO-Me inhibited cell survival Akt, NF-κB and mTOR signaling proteins. The inhibition of ROS generation by N-acetylcysteine (NAC) or by overexpression of antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase-1 (SOD-1) prevented CDDO-Me-induced apoptosis. Pretreatment with NAC blocked annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c by CDDO-Me. NAC also prevented the inhibition of constitutively active Akt, NF-κB and mTOR by CDDO-Me. Together, these data indicate that ROS plays an essential role in the induction of apoptosis by CDDO-Me in prostate cancer cells.     

N-乙酰半胱胺酸对高龄患者对比剂肾病的预防作用

目的 探讨N-乙酰半胱氨酸（N-acetylcysteine,NAC）对行增强CT检查的高龄患者对比剂肾病（contrast-induced nephropathy,CIN）的预防作用.方法 将行增强CT检查的高龄患者56例,采用随机数字表法随机分为NAC组28例、对照组28例.NAC组于增强CT检查前12 h、6 h,检查后6 h、12 h分别口服NAC泡腾片1 200 mg,2组均给予水化治疗,比较CT前后2组患者血肌酐和估算肾小球滤过率（estimated glomerular filtration rate,eGFR）变化,以及2组患者CIN发生率.结果 NAC组与对照组比较,增强CT检查后48 h,2组患者SCr水平均高于CT检查前（P＜0.01）,eGFR水平均低于CT检查前（P＜0.01）;检查前后NAC组SCr升高幅度与对照组比较差异无统计学意义（P＞0.05）,检查前、后NAC组eGFR下降幅度小于对照组,差异有统计学意义（P＜0.05）.NAC组无CIN发生,对照组仅有1例在行CT检查后SCr明显升高（SCr升高19.4 μmol/L,上升幅度28%）,但无临床意义,2组经校正的四格表χ2检验,差异无统计学意义（P＞0.05）.结论 NAC联合水化治疗对患者行增强CT所致CIN的预防作用与单纯水化治疗相当.说明大剂量NAC对对比剂引起的肾损害具有一定的防治作用.     

HPLC同时测定人血浆中乙酰半胱氨酸和谷胱甘肽浓度

目的 建立高效液相色谱法同时测定人血浆中乙酰半胱氨酸(NAC)和谷胱甘肽(GSH)浓度的方法.方法 采集血样,立即注入预加衍生化试剂DNTB的真空采血管中,25 min内分离血浆,以青霉胺为内标,10%三氯乙酸(TCA)沉淀蛋白,上清液进样20 μL.色谱柱为ZORBAX SB-C18(4.6 mm×250 mm,5 μm)及保护柱.流动相为0.05 mol·L-1乙酸钠缓冲液(pH 5.6)-甲醇(90:10),流速1 mL·min-1.柱温30 ℃,检测波长320 nm.结果 NAC和GSH在浓度3.05～61 μg·mL-1范围内呈良好的线性关系,NAC r=1(n=5),GSH r=0.999 8(n=5),检测限均为3.05 μg·mL-1.日内误差及日间误差RSD均在10%以内.低、中、高3个浓度的质控样品回收率在88.2%～101%之间.结论 该方法准确、快速、简便、重现性好,可供NAC的体内药动学研究.