N-乙酰半胱氨酸对重症急性胰腺炎大鼠肺损伤作用的实验研究

目的:探讨N-乙酰半胱氨酸(NAC)对重症急性胰腺炎(SAP)大鼠肺损伤的作用。方法:雄性SD大鼠30只,随机分为假手术组(SO组)、SAP组、NAC组。胆胰管逆行注射5%牛磺胆酸钠制备SAP模型,造模后30min腹腔注射5%NAC(0.2ml/100g)干预SAP模型,12h后处死大鼠。检测各组血清淀粉酶(AMY)、肺组织髓过氧化物酶(MPO)、胰腺和肺组织病理学评分、肺组织肿瘤坏死因子-α(TNF-α)和细胞间粘附分子-1(ICAM-1)mRNA表达的变化。结果:与SO组比较,SAP组AMY、MPO、胰腺和肺组织病理学评分明显升高(P<0.01),TNF-α和ICAM-1mRNA表达明显增强(P<0.01);应用NAC处理后,AMY和MPO水平下降,胰腺和肺组织损伤缓解,TNF-α和ICAM-1mRNA表达减弱,与SAP组有明显差异(P<0.01)。结论:NAC对SAP大鼠肺损伤具有保护作用,其机制可能与抑制肺组织TNF-α和ICAM-1mRNA的表达有关。     

N-乙酰半胱氨酸对早期日本血吸虫病小鼠肝脏虫卵肉芽肿的影响

目的 研究N-乙酰半胱氨酸（NAC）对早期日本血吸虫病小鼠肝脏虫卵肉芽肿的影响。 方法　 将36只健康小鼠随机分为NAC组、正常对照组、感染对照组。NAC组和感染对照组小鼠每只经腹部皮肤感染25±2条日本血吸虫尾蚴,于感染当天起给NAC组小鼠200 mg/kg NAC灌胃,2次/d,共42 d;正常对照组和感染对照组每只小鼠2 ml蒸馏水灌胃,2次/d,共42 d。感染第42天,各组小鼠全部处死后取血清和肝脏。对肝脏进行病理学观察,测定血清及肝组织的生化指标。 结果 NAC组小鼠的肝组织“+、++、+++”3级单个虫卵肉芽肿个数分别为1.80±0.25、1.37±0.23、0.53±0.15, 均显著低于感染对照组（P＜0.05）。NAC组小鼠血清中NO水平、GSH水平分别为0.53±0.17、229.66±9.47,相对感染对照组均有所下降（P＜0.05）,谷胱甘肽过氧化物酶GSH-PX活性为1101.99±140.81, 相对感染对照组有所升高（P＜0.05）;肝组织诱导型一氧化氮合酶（iNOS）活性、NO水平、还原型谷胱甘肽（GSH）水平及GSH-PX活性分别为6.85±0.30、13.44±0.40、358.40±19.15、110.84±10.93,均显著低于感染对照组（P＜0.05）。 结论 N-乙酰半胱氨酸可以减缓日本血吸虫病小鼠肝组织病理变化。     

N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology

Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer’s disease, Parkinson’s disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down’s syndrome have been associated with several mitochondrial alterations Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in cellular damage and programmed cell death. First, this review examines the mechanisms of action of N-acetylcysteine (NAC), an antioxidant and a free radical-scavenging agent that increases intracellular GSH, at the cellular level. NAC can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. The chemical properties of NAC include redox interactions particularly with other members of the group XIV elements (selenium, etc.) and ebselen, a lipid-soluble seleno-organic compound. Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule neurons. Recent findings on the protective effect of NAC against 4-hydroxynonenal (HNE)-induced toxicity in cerebellar granule neurons are summarized. Finally, the protective pharmacokinetics of NAC in humans and the possible usefulness of NAC for the treatment of neurodegenerative diseases are discussed with reference to basic and clinical studies.     

Protective effects of antioxidant medications on limb ischemia reperfusion injury

BACKGROUND: N-acetylcysteine, beta-glucan, and coenzyme Q(10) were shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on ischemia reperfusion injury of limb. MATERIAL AND METHOD: Forty-four New Zealand white rabbits, all female, weighing between 2.3 to 4.2 (mean 3.8) kg, were used in the study. Four study groups were arranged of 11 animals each, by randomization. The first group was the control group (Group C), the other groups were the Group Q, which was medicated with coenzyme Q10, the Group betaG, which was medicated with beta-glucan, and the Group N, medicated with N-acetylcysteine. After baseline measurements, for the ischemia-reperfusion experiments, common iliac artery was clamped and collateral flow was occluded by a rubber arterial tourniquet wrapped around the thigh at the proximal third of the leg. After 60 min of transient ischemic period, the limb was perfused for 180 min. After perfusion, biopsy was taken from the adductor magnus muscle. Second blood sampling was done after reperfusion period. Blood and tissue analysis were done and evaluated statistically. RESULTS: Baseline and post-reperfusion levels of glutathione peroxidase (GPx), super oxide dismutase (SOD), malonyldialdehyde (MDA), and nitric oxide (NO) changed significantly. While MDA levels increased in the control group, it decreased in the other study groups. The increase in GPx and SOD levels were significant in all groups except the control group. Levels of NO were found to have decreased in the control group, whereas it had increased in the other groups. CONCLUSION: Antioxidant medication may help lowering limb ischemia reperfusion injury. All mentioned medications in our study are shown to be able to have an effective role for preventing ischemia reperfusion injury to some extent through their antioxidant properties.     

Involvement of capsaicin-sensitive afferents and the Transient Receptor Potential Vanilloid 1 Receptor in xylene-induced nocifensive behaviour and inflammation in the mouse

The inflammatory actions of xylene, an aromatic irritant and sensitizing agent, were described to be predominantly neurogenic in the rat, but the mechanism and the role of the Transient Receptor Potential Vanilloid 1 (TRPV1) capsaicin receptor localized on a subpopulation of sensory nerves has not been elucidated. This paper characterizes the involvement of capsaicin-sensitive afferents and the TRPV1 receptor in nociceptive and acute inflammatory effects of xylene in the mouse. Topical application of xylene on the paw induced a short, intensive nocifensive behaviour characterized by paw liftings and shakings, which was more intensive in Balb/c than in C57Bl/6 mice. Genetic deletion of the TRPV1 receptor as well as destroying capsaicin-sensitive nerve terminals with resiniferatoxin (RTX) pretreatment markedly reduced, but did not abolish nocifensive behaviours. In respect to the xylene-induced plasma protein extravasation detected by Evans blue leakage, significant difference was neither observed between the Balb/c and C57Bl/6 strains, nor the ear and the dorsal paw skin. These inflammatory responses were diminished in the RTX pretreated group, but not in the TRPV1 gene-deleted one. Injection of the antioxidant N-acetylcysteine 15 min prior to xylene smearing significantly reduced plasma protein extravasation at both sites. These results demonstrate that xylene-induced acute nocifensive behaviour is mediated by capsaicin-sensitive afferents via TRPV1 receptor activation in mice. Neurogenic inflammatory components play an important role in xylene-induced plasma protein extravasation, but independently of the TRPV1 ion channel. Reactive oxygen or carbonyl species participate in this process presumably via stimulation of the TRPA1 channel.     

N-乙酰半胱氨酸对急性肺损伤大鼠环氧合酶2的影响

目的探讨N-乙酰半胱氨酸（N-acetylcysteine,NAC）对急性肺损伤（acute lung injury,ALI）大鼠环氧合酶2（cyclooxygenase-2,COX-2）的影响,进而研究NAC对ALI肺组织的保护作用。方法应用脂多糖诱导大鼠ALI模型,然后应用NAC进行干预。实验设对照组、模型组、NAC组,在肺损伤模型成功后24h处死大鼠,取左叶肺组织。采用免疫组化染色,检测NAC对急性肺损伤大鼠肺组织中COX-2表达的影响,利用HPIAS-2000图像分析系统测定COX-2在以上各组中表达的平均光密度和平均阳性面积率。结果实验中对照组肺组织中COX-2的表达较低;模型组肺组织中COX-2的表达高;NAC组肺组织中COX-2表达较低。经q检验,对照组与模型组之间,COX-2的平均光密度及阳性面积率有显著性差异（P〈0.01）,对照组与NAC组之间,COX-2的平均光密度及阳性面积率差异无显著性（P〉0.05）。结论NAC可以减轻肺损伤的程度,对急性肺损伤组织具有重要的保护作用。     

The effect of different treatment modalities on oxidative stress in COPD

INTRODUCTION: Oxidant/antioxidant interactions are known to be important processes in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of corticosteroids (CS), and Nacetylcysteine (NAC) on plasma oxidant/antioxidant levels in patients with COPD. METHODS: This study utilised a single-blind, randomised, placebo-controlled, parallel-group methodology. We enrolled 58 patients with stable COPD and 30 healthy controls with similar demographic profiles. The patients with COPD were randomly divided into three treatment groups. Group 1 received basal treatment (regular ipratropium bromide and beta-2 agonist as needed), placebo CS and placebo NAC. In addition to basal treatment, group 2 received oral CS (methylprednisolone 40 mg/day) and placebo NAC. Group 3 received basal treatment plus NAC (600 mg/day) and placebo CS. Each group received treatment for 15 days. We measured plasma malondialdehyde (MDA) and superoxide dismutase (SOD) at the start and the end of study. RESULTS: Post-treatment plasma MDA levels were significantly lowered only in group 2 (P=0.004). No significant differences were found with respect to erythrocyte SOD levels. CONCLUSION: This study demonstrates that oral CS, by aiding the oxidant/antioxidant system, may offer a new therapeutic option in COPD treatment.     

Effect of N-acetylcysteine on renal function in patients with chronic kidney disease

BACKGROUND: N-acetylcysteine (NAC) is commonly administered to high-risk individuals to attenuate the risk of contrast-induced nephropathy in spite of the debate regarding its efficacy. In several studies serum creatinine decreased after exposure to NAC and contrast dye. The mechanism by which NAC attenuates the decline in renal function is not known. Studies in subjects with normal renal function suggest NAC may have an effect on tubular secretion. AIM: The aim of this study was to determine the effect of NAC on renal function, measured by serum creatinine and Cystatin C, in patients with stage 3 chronic kidney disease. METHOD: Serum creatinine and Cystatin C were measured prior to, 4, 24 and 48 h after the administration of 600 mg oral NAC in 30 patients. The protocol was repeated with the addition of 1200 mg oral cimetidine administered 3 h before NAC. RESULTs: Serum creatinine was not significantly different from baseline (186 +/- 65 micromol/L) to 4 h (185 +/- 62 micromol/L), 24 h (187 +/- 64 micromol/L) or 48 h (184 +/- 61 micromol/L) post NAC, nor were Cystatin C levels. Co-administration of cimetidine resulted in a significant rise in serum creatinine with no change in Cystatin C levels. CONCLUSION: This study failed to detect a change in serum creatinine or Cystatin C after a single dose of NAC in participants with stage 3 chronic kidney disease. Further randomized trials of multiple doses and longer follow up are needed to confirm these results.     

Protective effect of N-acetylcysteine against BDE-209-induced neurotoxicity in primary cultured neonatal rat hippocampal neurons in vitro

Globally, brominated diphenyl ether-209 (BDE-209) is the most widely used polybrominated diphenyl ether (PBDEs). It has been reported that BDE-209 induces developmental neurotoxicity in vivo. The purpose of this study was to use an antioxidant, N-acetylcysteine (NAC), as an antidote for the neurotoxic effect of BDE-209. We used primary hippocampal neurons from rats for the in vitro cultures. BDE-209 was added to the cultures in increasing concentrations and co-cultured with NAC in order to assess the effect of NAC on BDE-209-induced neurotoxicity. We measured cell viability, apoptosis, expression of phosphorylated p38 mitogen-activated protein kinases (MAPK), intracellular calcium content, and intracellular reactive oxygen species (ROS) levels. The difference between the BDE-209 groups without NAC and the blank control groups was significant (P < 0.05). The difference between the NAC treatment groups and the BDE-209 groups without NAC was also significant (P < 0.05), showing that BDE-209 increased apoptosis, the expression of p38 MAPK, the calcium ion concentration, and the ROS level and decreased cell viability. In contrast, NAC reduced the degree of cellular cytotoxicity induced by BDE-209. The results suggested that NAC may be able to attenuate BDE-209-induced neurotoxicity.     

Effects of phenylethyl isothiocyanate and its metabolite on cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells

Abstract

Cruciferous vegetable consumption is associated with decreased risk of several cancers, including prostate cancer. Gluconasturtiin, one of the predominant glucosinolates in cruciferous vegetables, is hydrolyzed to yield phenylethyl isothiocyanate (PEITC). PEITC absorption and metabolism in humans involves glutathione conjugation followed by conversion via the mercapturic acid pathway to an N-acetylcysteine (NAC) conjugate that is excreted in the urine. We observed an inhibitory effect of PEITC and its metabolite, NAC-PEITC, on cancer cell proliferation, cell-cycle progression, and apoptosis in LNCaP human prostate cancer cells. PEITC and NAC?PEITC suppressed LNCaP cell proliferation in a dose-dependent manner, and exposure to 5 μM PEITC or NAC-PEITC reduced cell proliferation by 25% and 30%, respectively. Cell-cycle analysis revealed that cells treated with 5 μM PEITC or NAC-PEITC arrested at the G₂/M phase. In addition, the percentage of cells in the S phase decreased from 46% to 25% following 48 h of incubation with PEITC or NAC-PEITC. The G₂/M-phase cell-cycle arrest of LNCaP cells grown in the presence of PEITC or NAC-PEITC is correlated with the downregulation of Cdk1 and cyclin B₁ protein expression. Apoptosis was observed at the later stages of 24-h and 48-h treatments with 5 μM PEITC and NAC-PEITC. In conclusion, PEITC and NAC-PEITC are potential chemopreventive/chemotherapeutic agents against LNCaP human prostate cancer cells.