Effects of N-acetylcysteine on bacterial clearance

Abstract. The aim of this study was to investigate whether the oxygen radical scavenger N -acetylcysteine ( N -AC) impairs bacterial clearance, thus predisposing the host to increased risk of disease. Blood clearance of Escherichia coli and organ colonization were investigated in anaesthetized rabbits after pretreatment with N -AC (250 mg kg^-1 body weight, n = 16) and in sham-operated animals ( n = 12). To enable quantification of the clearance process, defined numbers of exogenous E. coli [1.3 times 108 colony-forming units (CFUs)] were injected intravenously. Parameters monitored were kinetics of bacterial elimination from the blood, and polymorphonuclear leucocyte (PMN) oxidative burst activity. Samples of liver, kidney, spleen and lung were collected for bacterial counts. Compared with controls, pretreatment with N -AC resulted in delayed bacterial elimination from blood and higher organ colonization with increased numbers of E. coli in liver, lung and kidney ( P < 0.05). N -AC treatment was associated with a suppressed PMN oxidative burst activity. Impaired bacterial clearance and enhanced organ colonization in N -AC-treated animals correlated with reduced oxidative burst activity, suggesting impaired granulocyte-dependent bacterial killing due to N -AC application.     

N-乙酰半胱氨酸对慢性阻塞性肺疾病患者血淋巴细胞DNA损伤的影响

目的　探讨N -乙酰半胱氨酸 (NAC)治疗不同病期慢性阻塞性肺疾病 (COPD)的疗效。方法　 49例稳定期、急性发作期COPD患者 ,随机分为观察组 (2 5例 )和对照组 (2 4例 ) ,观察组除给予常规治疗外 ,加用NAC(每次 2 0 0mg ,3/d ,连用 2个月 ) ;对照组仅给予常规治疗。治疗前后观察所有患者外周血淋巴细胞DNA损伤程度。结果　治疗前后比较 ,观察组稳定期、急性发作期DNA损伤明显降低 ,差异有显著性 (P <0 .0 5)。对照组稳定期DNA损伤程度亦有一定程度的改善 ,但差异无显著性 (P >0 .0 5) ,急性发作期DNA损伤程度降低 ,差异有显著性 (P <0 .0 5)。结论　COPD患者体内存在氧化 -抗氧化失衡 ,抗氧化治疗可降低COPD患者外周血淋巴细胞DNA损伤程度 ,急性发作期出现氧化应激。     

Effect of NMDA on Production of Reactive Oxygen Species by Human Lymphocytes

Low concentrations (<20 M) of N-methyl-D-aspartate (NMDA), an agonist of specific receptors of brain glutamatergic systems, promote the formation of reactive oxygen species (ROS) both in the whole blood and in lymphocyte fraction. Further increase in NMDA concentrations led to progressive increase in ROS content in the whole blood, but to its decrease in lymphocyte suspension. The activating effect of NMDA is abolished by antioxidant N-acetylcysteine (5 mM) and NMDA-type glutamate receptor antagonist MK-801 (5 M). Phorbol myristate acetate (PMA, 1 M) also increased ROS content in the examined structures. This effect was antagonized by N-acetylcysteine, but not MK-801.     

Development and in Vitro Evaluation of Systems to Protect Peptide Drugs from Aminopeptidase N

Purpose. Develop and evaluate systems to prevent aminopeptidase N caused enzymatic degradation of perorally administrated peptide drugs. Methods. Bacitracin was covalently bound to the unabsorbable carrier matrix poly(acrylic acid) (paa) in order to avoid any dilution effects of the inhibitor in the intestine as well as systemic toxic side effects. The inhibitory effect of this conjugate, of neutralized paa and N-acetylcysteine was evaluated using a brush border membrane model. Results. Whereas within 6 h of incubation 65.3 ± 3.7 mol/1 of the substrate (L-leucine p-nitroanilide) was hydrolyzed under our assay conditions, this metabolism was reduced to 44.5 ± 6.3 mol/1 and 49.0 ± 8.8 mol/1 (n = 3–5; ± S.D.) using 1.5% bacitracin-polymer conjugate and 0.5% N-acetylcysteine, respectively. The same amount of bacitracin as immobilized to the polymer exhibited a comparably weaker inhibitory effect. Neutralized paa did not inhibit membrane bound aminopeptidase N. Covering the membrane with a thin mucus layer led to a significantly lowered inhibitory effect of all tested agents. Conclusions. The immobilization of enzyme inhibitors to a carrier matrix and the use of N-acetylcysteine as a novel inhibitor are promising strategies in order to overcome the enzymatic barrier caused by membrane bound peptidases. However the use of effective mucolytic agents seems to be a prerequisite.     

N-乙酰半胱氨酸和氯胺酮联用对脑缺血再灌注损伤的影响

目的:研究巯基供体物质N 乙酰半胱氨酸(NAC)和非竞争性NMDA受体拮抗剂氯胺酮(KT)联用对小鼠脑缺血再灌注损伤的影响。方法:雄性ICR小鼠,随机分为假手术组、生理盐水组(0 .0 1L·g- 1)、氯胺酮组(15mg·kg- 1)、N 乙酰半胱氨酸组(75mg·kg- 1)和联合组(KT 15mg·kg- 1 NAC75mg·kg- 1)。参照蒋晓帆等建立的方法,制备局灶性短暂性脑缺血再灌注模型(tMCAO) ,再灌注后6、2 4h测定神经行为缺陷评分,处死TTC染色测定脑梗死面积百分比;制备不完全性脑缺血再灌注模型(2 VO) ,在再灌注0 .5、2和6h时取全脑制成10 %匀浆,比色法测定MDA含量、SOD和GSH Px活力。结果:(1)短暂性局灶性脑缺血再灌注后6、2 4h ,各组小鼠脑组织均有不同程度梗死灶、神经行为缺陷明显,与生理盐水组比较,药物联合组可显著改善缺血再灌注小鼠的神经行为缺陷(均为P <0 .0 1) ,减少脑梗死面积百分比(均为P <0 .0 1) ,药物单用对以上指标有轻度的改善作用(P >0 .0 5 )。(2 )联合用药可明显改善脑细胞损伤。(3)与假手术组比较,不完全性全脑缺血再灌注损伤0 .5、2和6h后,生理盐水组小鼠MDA含量显著升高(均为P <0 .0 1) ,SOD活性(均为P <0 .0 1)和GSH Px活性均显著降低(均为P <0 .0 1)。与生理盐水组比较,联合组可显著地降低缺血再灌注小鼠脑组织     

乙酰半胱氨酸对小鼠酒精中毒的影响

目的 :观察5 %N—乙酰—L—半胱氨酸 (NAC)口服液对小鼠醉酒后血清乙醇浓度和肝、胃组织乙醇脱氢酶活性的影响。方法 :用生理盐水或5 %NAC口服液灌服小鼠30min后 ,再灌服白酒 ,记录小鼠翻正反射消失 (醉酒 )至恢复 (醒酒 )所需时间及24h内小鼠的死亡只数 ;另对小鼠以相同灌服方法连续6d灌服后眼眶取血并处死小鼠 ,立即取出其肝脏和胃 ,分别用生化比色法测定血清乙醇浓度和肝、胃组织乙醇脱氢酶活性。结果 :在醉酒实验中 ,与对照组比较 ,服用5 %NAC口服液组小鼠从饮酒到醉酒的时间明显延长 (P<0 01) ,醒酒时间明显缩短 ,且小鼠的死亡率明显降低 (P<0 05) ;服用5 %NAC口服液组小鼠血清乙醇浓度明显低于单纯服用白酒的小鼠 (P<0 01)。结论 :5 %NAC口服液具有解酒作用。     

N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with pre-existing renal insufficiency or diabetes: a systematic review and meta-analysis

Abstract

Purpose: To identify benefit of N-acetylcysteine (NAC) on patients with pre-existing renal insufficiency or diabetes. Background: NAC administration is a common method for prevention of contrast-induced nephropathy (CIN). Nevertheless, its benefit on patients with pre-existing renal insufficiency or diabetes remains uncertain and controversial. Methods: Randomized controlled trials (RCTs) to evaluate the efficacy of NAC for the prevention of CIN in patients with pre-existing renal insufficiency or diabetes were searched from the databases of MEDLINE, EMBASE, and Cochrane library. Pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated using fixed-effects model by the Mantel–Haenszel test. Results: Twenty RCTs involving 3466 subjects (1756 assigned to NAC and 1710 assigned to the control) were included in the pre-existing renal dysfunction group. Pooled analysis suggested a significant reduction in CIN among this group (OR, 0.76; 95% CI, 0.61–0.93; p?=?0.008). However, the nine trials comparing NAC versus control among patients with diabetes (NAC, 367 subjects; control, 358 subjects) showed no benefit of NAC for prevention of CIN (OR?=?0.87; 95% CI, 0.58–1.30; p?=?0.50). No significant heterogeneity was detected (p?=?0.07; I²?=?34% for the group of pre-existing renal dysfunction; p?=?0.40; I²?=?5% for the group of diabetes). Conclusion: Our results suggest that NAC decreases the incidence of contrast-induced nephropathy among patients with pre-existing renal insufficiency. The benefit was not existed in patients with diabetes.     

N-acetylcysteine protects against star fruit-induced acute kidney injury

Background: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect.

Materials and methods: Male Wistar rats received SF juice (4?mL/100?g body weight) by gavage after a 12?h fasting and water deprivation. Fasting and water deprivation continued for 6?h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n?=?6): received tap water; SF?+?NAC (n?=?6): received NAC (4.8?g/L) in drinking water for 48?h after gavage; and Sham (n?=?6): no interventions. After 48?h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments.

Results: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy.

Conclusions: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.     

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.     

N-乙酰半胱氨酸对心肺转流下心脏直视手术患者肺功能的影响

目的观察N-乙酰半胱氨酸(N-acetylcysteine,NAC)对心肺转流(cardiopulmonary bypass,CPB)下心脏直视手术患者肺功能参数的影响。方法择期在CPB下行心脏瓣膜置换术的风湿性心脏病患者40例,性别不限,年龄40~65岁,体重45~80kg,ASAⅡ或Ⅲ级,心功能Ⅰ~Ⅲ级,随机均分为NAC组和对照组(C组)。NAC组:麻醉诱导后CPB前静脉输注NAC 100mg/kg,CPB开始后静脉持续输注NAC 40mg/kg至术毕。C组:等剂量用生理盐水作为安慰剂静脉输注。于麻醉诱导后(T0)、开胸后CPB前(T1)、术毕关胸后(T2)、术后5h(T3)、24h(T4)和48h(T5)检测呼吸指数(RI)、氧合指数(OI)、肺泡-动脉氧分压差(A-aDO2)和气道阻力(R)。结果与T0时比较,T2~T4时两组患者RI、A-aDO2明显升高(P0.05)、OI明显降低(P0.05)、T2和T3时两组患者气道阻力明显升高(P0.05)。与C组比较,T2~T4时NAC组RI和A-aDO2明显降低(P0.05)、OI明显升高(P0.05)、T2和T3时NAC组气道阻力明显降低(P0.05)。结论 N-乙酰半胱氨酸可以减轻CPB导致的肺功能损伤,对肺脏可能具有保护作用。