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.     

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.     

N-乙酰半胱氨酸预防亚硒酸钠诱导大鼠白内障的研究

目的：对亚硒酸钠诱导白内障大鼠采用N-乙酰半胱氨酸进行预防性治疗,探讨N-乙酰半胱氨酸对白内障大鼠模型氧化损伤和晶状体浑浊程度的影响。方法30只SD乳鼠随机分为3组,模型组ip 3.46 mg/kg亚硒酸钠溶液造模后,ip 0.1 mL/10 g生理盐水;实验组ipN-乙酰半胱氨酸10 mg/g,30 min ip亚硒酸钠溶液造模;对照组ip 0.1 mL/10 g生理盐水。所有动物均为隔日注射,连续6次。比较大鼠晶状体浑浊程度和SOD活性、NOS活性和MDA水平。结果在晶状体核区、后囊区、前囊区＋后囊区、前囊区＋皮质区＋核区＋后囊区中,实验组与模型组比较得分差异具有统计学意义（P＜0.05）;实验组SOD活性和MDA活性与模型组比较差异均具有统计学意义（P＜0.05）。结论 N-乙酰半胱氨酸能够预防后囊和核区白内障的发生,其作用是通过减少MDA水平、提高SOD活性、改善氧化应激实现的。     

N-乙酰半胱氨酸对大鼠急性脊髓损伤后继发性脊髓损伤的保护作用

目的 探讨N-乙酰半胱氨酸(NAC)对大鼠脊髓急性损伤后继发性脊髓损伤的保护机制.方法 成年SD大鼠18只随机均分成单纯椎板切除(对照组)、急性脊髓损伤(损伤组)和急性脊髓损伤后NAC治疗(治疗组)三组.用30 g力量动脉瘤夹从两侧夹闭脊髓30 s建立脊髓损伤模型.治疗组术后15 min、1、2和3d分别予NAC 150 mg/kg腹腔注射;对照组和损伤组腹腔注射等量生理盐水.所有动物于术后3d处死取材,用凝胶电泳迁移率分析和免疫组化检测脊髓组织中核因子κB(NF-κB),ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-6表达.结果 损伤组脊髓组织中NF-κB、TNF-α、IL-1β和IL-6水平均比对照组升高(P＜0.05),治疗组脊髓组织中各因子水平均比损伤组显著降低(P＜0.05).结论 NAC可以通过抑制大鼠急性脊髓损伤后NF-κB的活性,进一步下调TNF-α、IL-1β和IL-6的表达,从而减轻继发性炎症反应所导致的脊髓损伤.     

MMP-9/TIMP-1在脂多糖和N-乙酰半胱氨酸干预体外孵育胎膜中的表达及意义

目的探讨感染引发早产的可能机制及N-乙酰半胱氨酸(NAC)预防感染引发早产的可行性。方法取20例正常择期剖宫产孕妇(无妊娠合并症及临产征兆)的胎膜在体外进行孵育,共分成5组:0 h组(取下后未经孵育的胎膜),24 h组,48 h组,72 h细菌内毒素脂多糖组(LPS组),72 h LPS NAC组(LPS NAC组)。首先评价体外孵育胎膜的存活力,然后应用逆转录聚合酶链反应(RT-PCR)分别测定5组胎膜的基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制因子-1(TIMP-1)mRNA表达水平的变化,最后比较LPS组和LPS NAC组MMP-9/TIMP-1比值的变化。结果体外孵育胎膜的存活力达到83%±1.9%,RT-PCR可见0 h组及48 h组的MMP-9表达微弱,24 h组的表达较前两组增强(P<0.05),LPS组的表达最强(与24 h组比较P<0.01),LPS NAC组的表达低于LPS组(P<0.01),各组TIMP-1的表达无明显区别(P>0.05),LPS NAC组较LPS组MMP-9/TIMP-1比值明显降低(P<0.01)。结论MMP-9/TIMP-1比值升高可能是感染引发早产的机制之一,NAC有望在预防和治疗早产中发挥作用。     

N-乙酰半胱氨酸联合甲基强的松龙治疗放射性肺损伤临床研究

目的探讨使用N-乙酰半胱氨酸(NAC)治疗放射性肺损伤的临床效果和应用价值。方法将100例放射性肺损伤患者随机平均分为甲基强的松龙治疗组(对照组)和甲强龙+N-乙酰半胱氨酸治疗组(治疗组),每组50例,疗程14天。4周后观察2组临床疗效。并分别于第1天和第14天观察血浆TNF-α、IL-6、TGF-β1和CRP水平变化。结果 4周后甲强龙治疗组总有效率为78%,甲强龙+N-乙酰半胱氨酸治疗组为88%,两组间临床疗效的差异有统计学意义(χ2=4.461,P<0.05)。2治疗组在第1天时血浆TNF-α、IL-6、TGF-β1和CRP水平无统计学差异(P均>0.05)。在第14天时,2治疗组血浆TNF-α、IL-6、TGF-β1和CRP水平较前明显下降,各指标差异均有统计学意义(P均<0.05)。同时,与甲强龙治疗组相比甲强龙+N-乙酰半胱氨酸组血浆TNF-α、IL-6、TGF-β1和CRP水平下降更明显,差异均有统计学意义(P均<0.05)。结论本研究发现在常规使用甲强龙治疗的基础上加用N-乙酰半胱氨酸进行辅助治疗,能有效减轻放射性肺损伤的临床症状,同时降低血浆TNF-α、IL-6、TGF-β1和CRP水平。N-乙酰半胱氨酸对于放射性肺损伤有保护作用,可常规应用于临床治疗。     

糖尿病大鼠SOD活性及蛋白表达水平抗氧化剂N-乙酰半胱氨酸对糖尿病大鼠心、肺、肝、肾组织中的组织差异性及抗氧化剂治疗对机体抗氧化状态SOD活性及蛋白表达的影响

摘 要 目的 探究糖尿病大鼠主要脏器SOD活性及蛋白表达水平的变化,并观察抗氧化剂N-乙酰半氨胺酸（N-acetylcysteine,NAC）短期治疗（4周）后对机体抗氧化状态的影响。方法 STZ诱导的糖尿病大鼠（D组,n＝8）每天给予NAC 1.5g/kg灌胃治疗（D T组,n＝8）,正常对照组（C组,n＝8）同时给予同体积生理盐水。4周后,获取心、肺、肝、肾组织,试剂盒检测血浆总SOD、总抗氧化物浓度、脂质过氧化特异性标志物15-F2t-isoprostane及各组织总超氧化物歧化酶（superoxide dismutase,SOD）活性,Western blotting分析SOD亚型Cu/Zn-SOD及Mn-SOD蛋白表达水平。结果 与C组相比,D组大鼠血浆15-F2t-isoprostane与总抗氧化物浓度及心肌组织中总SOD活性显著升高,其它组织显著降低而血浆、肺、肝、肾组织总SOD活性显著降低;心、肺组织中Cu/Zn-SOD蛋白表达水平明显升高,而肝、肾组织中明显降低;肺、肾组织中Mn-SOD蛋白表达水平明显降低,而肝组织明显升高,但心肌组织变化不明显。NAC干预能不同程度逆转上述改变,但进一步降低肾组织Mn-SOD表达。结论 糖尿病大鼠各组织中抗氧化剂NAC对总SOD活性、Cu/Zn-SOD及Mn-SOD蛋白表达水平具有组织差异性,抗氧化剂NAC的影响程度与组织种类相关,能不同程度恢复糖尿病大鼠各组织总SOD活性抗氧化水平,从而起到阻止或延缓糖尿病相关的靶器官功能损害的作用。     

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.     

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。