Influence Of N-acetylcysteine Research Articles

N-acetylcysteine effectively alleviates systemic lupus erythematosus in mice via regulation of oxidative stress

Purpose: To study the influence of N-acetylcysteine (NAC) on systemic lupus erythematosus (SLE) mice, and the mechanism(s) involved.
 Methods: Fourteen MRL/lpr SLE mice aged 5 weeks (mean weight = 20.35 ± 2.12 g) were divided into two 7-mouse groups: SLE (control) and treatment groups. The control group comprised healthy female SPF-grade C57BL/6 mice (n = 7). The treatment group mice received intraperitoneal injection of NAC at a dose of 250 mg/kg daily for 8 weeks. The serum levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), were assayed using standard methods. The level of urine protein and activity of anti-double stranded (ds) DNA antibody were determined using their respective enzyme-linked assay (ELISA) kits.
 Results: The spleens of mice in SLE mice were significantly enlarged, relative to control mice, but they were reduced significantly by NAC (p < 0.05). N-Acetylcysteine (NAC) also significantly reduced the serum levels of MDA and NO in SLE mice, but significantly increased the serum activities of superoxide dismutase and GPx. Moreover, urine protein concentration and activity of anti-dsDNA antibody in SLE mice significantly increased, but reduced significantly by NAC treatment (p < 0.05).
 Conclusion: These results suggest that NAC effectively alleviates SLE in mice via regulation of oxidative stress. Thus, NAC has the potentials for development into a therapy for the management of SLE.
 Keywords: Anti-dsDNA antibodies, Antioxidant enzymes, N-acetylcysteine, Oxidative stress, Systemic lupus erythematosus

The Influence of N-Acetylcysteine Alone and in Combination with Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Antagonist on Systemic and Tissue Levels in Rats with Experimentally-Induced Chronic Renal Failure

The Influence of N-Acetylcysteine Alone and in Combination with Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Antagonist on Systemic and Tissue Levels in Rats with Experimentally-Induced Chronic Renal Failure

Influence of N-acetylcysteine on FEV1, VC, DLCO, PaO2 in patients with chronic obstructive pulmonary disease and pulmonary interstitial fibrosis

Objective To investigate the influence of N-acetylcysteine on forced expiratory volume in one second(FEV1), vital capacity(VC), diffusion capacity of lung carbon monoxide(DLCO), arterial oxygen partial pressure(PaO2) in patients with chronic obstructive pulmonary disease(COPD) and pulmonary interstitial fibrosis. Methods From January 2015 to July 2017, 140 COPD patients complicated with pulmonary interstitial fibrosis in the People's Hospital of Shanxi Province were chosen as study objects, and they were divided into control group and research group according to the digital table, with 70 cases in each group.The control group was treated with routine treatment, while the research group was treated with N-acetylcysteine.After treatment, the treatment effects, VC, FEV1, PaO2, DLCO, TGF-β and VEGF between the two groups were compared. Results The total effective rate of the research group was 82.86%(58/70), which of the control group was 58.57%(41/70), the difference was statistically significant (χ2=9.968, P 0.05). After treatment, the FEV1[(59.03±15.02)% vs.(53.35±13.71)%], VC[(69.95±11.83)% vs.(65.21±11.65)%], DLCO[(68.92±11.56)% vs.(64.01±11.34)%] and PaO2[(68.79±5.38)mmHg vs.(62.37±6.14)mmHg]of the research group were higher than those of the control group, the differences were statistically significant (t=2.337, 2.389, 2.537, 6.580, all P 0.05). After treatment, the VEGF[(0.32±0.04)ng/L vs.(0.44±0.05)ng/L] and TGF-β[(271.16±35.21)ng/L vs.(345.13±39.08)ng/L] levels of the research group were lower than those of the control group, the differences were statistically significant (t=11.765, 15.680, all P 0.05). Conclusion Large dose of N-acetylcysteine can effectively improve the TGF-β and VEGF levels of COPD patients complicated with pulmonary interstitial fibrosis, and promote its pulmonary function, with good safety. Key words: Pulmonary fibrosis; Pulmonary disease, chronic obstructive; Vital capacity; Vascular endothelial growth factor; Transforming growth factor; Arterial oxygen partial pressure; Diffusion capacity of lung carbon monoxide; N-acetylcysteine

N-acetylcysteine attenuates neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat.

Depression is a heterogeneous disorder and associated with inflammatory responses. The influences of N-acetylcysteine (NAC) on neuroinflammation associated depression-like behavior have not been investigated yet, and associated biochemical changes are currently unclear. Therefore, we assessed the effects of NAC on neuroinflammation associated depression-like behavior induced through chronic unpredictable mild stress (CUMS) in rats. The antidepressant-like effect of NAC was depicted using the sucrose preference test and the forced swimming test (FST) while CUMS-induced alteration in the locomotor index was measured using the open field test (OFT) and actophotometer. Our results revealed that CUMS exposure markedly aggravated depression-like behavior, the levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and reduced the serotonin levels. One-week consecutive NAC (50 and 100 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o., a selective serotonin reuptake inhibitor) treatment significantly increased sucrose preference index, reduced immobility time in the FST, and the increased the number of squares crossed, number of rearing in the OFT and locomotion in the actophotometer in the CUMS-exposed rats. Moreover, the levels of pro-inflammatory cytokines in the hippocampus as well as pre-frontal cortex were suppressed, and remarkably restored the serotonin levels by NAC (50 and 100 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.) administration. However, NAC (25 mg/kg, p.o.) exerted insignificant protection against CUMS-induced depressive-like behavior and associated neuro-inflammation. This study demonstrates that NAC exhibited the antidepressant-like effect in the CUMS-exposed rats, which might be mediated by anti-inflammatory potential and restoring serotonergic responses in the stressed rats.

Synergistic enhancement of production of proinflammatory cytokines of human peripheral blood monocytes by anti-Sm and anti-RNP antibodies.

The present study was performed to elucidate the roles of serum anti-Sm antibodies in the pathogenesis of systemic lupus erythematosus (SLE). Highly purified peripheral blood monocytes obtained from healthy donors were cultured in the presence of monoclonal anti-Sm antibody (anti-Sm mAb), monoclonal anti-U1-RNP antibody (anti-RNP mAb) or control murine IgG1 or IgG3. After various periods of incubation, levels of IL-6 and TNF-α in the culture supernatants were measured by ELISA and the expression of mRNA for various molecules in monocytes was determined using RT-PCR. Flow cytometry analysis confirmed the bindings of anti-Sm mAb and anti-RNP mAb on viable human monocytes. Both anti-Sm mAb and anti-RNP mAb significantly increased the production of IL-6 and TNF-α of human monocytes in a dose-dependent manner, although the latter was more potent than the former. Of note, anti-Sm mAb synergistically enhanced the production and mRNA expression of IL-6 and TNF-α of human monocytes in the presence of anti-RNP mAb. Notably, anti-RNP mAb, but not anti-Sm mAb, significantly enhanced the mRNA expression of RelA in human monocytes. Finally, anti-Sm mAb still up-regulated the IL-6 production of monocytes in the presence of anti-RNP mAb under the influence of N-acetyl cysteine or pyrrolidine dithiocarbamate that totally abrogated the IL-6 production provoked by anti-Sm mAb alone in the absence of anti-RNP mAb. These results demonstrate that anti-Sm and anti-RNP antibodies synergistically up-regulate the expression of IL-6 and TNF-α in human monocytes. The data also suggest that the effect of anti-Sm in the synergy with anti-RNP might not involve NFkB activation.

N-acetyl-cysteine increases the replication of Chlamydia pneumoniae and prolongs the clearance of the pathogen from mice.

Purpose. Within the community, 10 % of acquired pneumonia is caused by Chlamydia pneumoniae. N-acetyl-cysteine (NAC) is one of the most commonly used mucolytics in respiratory diseases, but its effect on C. pneumoniae infection has not yet been investigated. In this study, our aim was to investigate whether NAC influences the replication of C. pneumoniae. After determining that NAC does have an effect on C. pneumoniae replication, the effect of an alternative drug called Ambroxol (Ax) was investigated.Methodology. The in vitro effect of NAC and Ax was studied on C. pneumoniae-infected A549 and McCoy cells. Furthermore, the influence of NAC and Ax was examined in mice infected intranasally with C. pneumoniae.Results. NAC treatment resulted in approximately sixfold more efficient C. pneumoniae growth in tissue culture compared to the untreated control cells, and this effect was shown to be based on the increased binding of the bacterium to the host cells. The C. pneumoniae-infected mice to which NAC was given had prolonged and more severe infections than the control mice. Ax decreased C. pneumoniae replication in vitro, which was partially associated with the increased expression of indolamine 2,3-dioxygenase. In animals, using the adapted usual human dose, Ax did not alter the number of recoverable C. pneumoniae.Conclusion. Based on our results, it might be recommended that a mucolytic agent other than NAC, such as Ax, be used in respiratory diseases suspected to be caused by C. pneumoniae.

Influence of N-acetyl cysteine on beta-amyloid-induced Alzheimer's disease in a rat model: A behavioral and electrophysiological study.

Alzheimer's disease is an age-related neurodegenerative disorder characterized by a progressive decline in cognitive function due to the extracellular accumulation and deposition of beta-amyloid peptide (Aβ). The purpose of this study was to evaluate the protective effect of N-acetyl cysteine (NAC) on learning and memory in an Aβ-induced Alzheimer's disease model in adult male rats, using behavioral and electrophysiological methods Thirty-five rats were divided into five groups: control, sham-operated, Aβ, Aβ+NAC (1-14days), and Aβ+NAC (14-28days). Learning and memory were evaluated behaviorally using the passive avoidance test and electrophysiologically by assessing hippocampal long-term potentiation, a cellular mechanism of learning and memory. Intrahippocampal Aβ injections reduced step-through latency in the passive avoidance test, and decreased both the amplitude of hippocampal neuron population spikes and the slope of excitatory postsynaptic potentials, compared to the sham and control groups. Administration of NAC in rats receiving Aβ alleviated the Aβ-induced deficits in comparison to the Aβ-only group. The results of this study suggest that NAC shows potential for treatment of Alzheimer's disease.

Influence of N-Acetyl Cysteine on Early Graft Outcome of Recipient in Live Donor Liver Transplantation: A Double Blind Randomised Controlled Trial

Influence of N-Acetyl Cysteine on Early Graft Outcome of Recipient in Live Donor Liver Transplantation: A Double Blind Randomised Controlled Trial

Influence of acetylcysteine on cytogenetic effects of etoposide in mouse oocytes

The influence of N-acetylcysteine (ACC) on the cytogenetic effects of etoposide in F1 CBA x C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has a dose-dependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in oocytes of 6-, 9-, and 12-week-old mice during triple introduction at a dose 200 mg/kg per os. The most pronounced anticlastogenic ACC activity (an 80% decrease) was registered in 9-week-old females; a 100% decrease in aneugenesis was detected in 6-week-old female mice.

N-Acetyl Cysteine Depletes Reactive Oxygen Species and Prevents Dental Monomer-Induced Intrinsic Mitochondrial Apoptosis In Vitro in Human Dental Pulp Cells.

PurposeTo investigate the involvement of intrinsic mitochondrial apoptosis in dental monomer-induced cytotoxicity and the influences of N-acetyl cysteine (NAC) on this process.MethodsHuman dental pulp cells (hDPCs) were exposed to several dental monomers in the absence or presence of NAC, and cell viability, intracellular redox balance, morphology and function of mitochondria and key indicators of intrinsic mitochondrial apoptosis were evaluated using various commercial kits.ResultsDental monomers exerted dose-dependent cytotoxic effects on hDPCs. Concomitant to the over-production of reactive oxygen species (ROS) and depletion of glutathione (GSH), differential changes in activities of superoxide dismutase, glutathione peroxidase, and catalase were detected. Apoptosis, as indicated by positive Annexin V/propidium iodide (PI) staining and activation of caspase-3, was observed after dental monomer treatment. Dental monomers impaired the morphology and function of mitochondria, and induced intrinsic mitochondrial apoptosis in hDPCs via up-regulation of p53, Bax and cleaved caspase-3, and down-regulation of Bcl-2. NAC restored cell viability, relieved oxidative stress and blocked the apoptotic effects of dental monomers.ConclusionsDental monomers induced oxidative stress and mitochondrial intrinsic apoptosis in hDPCs. NAC could reduce the oxidative stress and thus protect hDPCs against dental monomer-induced apoptosis.

The influence of N-acetylcysteine on the cytotoxicity of single-walled carbon nanotubes in human lung carcinoma cells

The influence of N-acetylcysteine on the cytotoxicity of single-walled carbon nanotubes in human lung carcinoma cells

Influence of N-Acetylcysteine on Oxidative Stress in Slow-Twitch Soleus Muscle of Heart Failure Rats

Background: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. Methods and Results: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47^phox was lower in MI-C than Sham. NAC decreased NOX4 and p22^phox expression. Conclusions: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.

Abstract 656: N-acetylcystein Reduces Lipid Peroxidation and Advanced Glycation Related to Prevention of Macrophage Endoplasmic Reticulum Stress Induced by Albumin Isolated from Rats With Chronic Kidney Disease

Objective: We analyzed the influence of N-acetylcysteine (NAC) in chronic kidney disease (CKD) rats on the plasma concentration of lipid peroxides (TBARS) and advanced glycation end products (AGE) and on the impact of serum CKD-albumin in the development of macrophage endoplasmic reticulum stress (ERS). Methods: CKD was induced by 5/6 nephrectomy in 2-month old male Wistar rats. Controls (C) were sham operated. Animals were treated or not with NAC (600mg/L of water). FPLC isolated serum albumin was purified by alchoolic extraction. J774 macrophages were incubated with serum albumin (1mg/mL; 18h) from all groups, and the expression of ERS markers (protein disulfide isomerase - PDI and Grp94 chaperone) determined by immunoblot. Comparisons were done by one-way ANOVA, Student t test. Results: After 60 days of CKD, body weight was 10% lower in CKD compared to C (p<0.01). This was prevented by NAC. Urea, creatinine, total cholesterol (TC), triglycerides (TG) (mg/dL), urinary protein excretion (mg/24h) (C, n= 31; C+NAC, n=20; CKD, n=74; CKD+NAC, n=32), total AGE and pentosidine (n= 8; fluorescence arbitrary unit) and TBARS (n= 7; nmoL/mL) were higher in CKD (122±8; 0.9±0.07; 151±6; 83±4; 46±2.5; 32620±673; 16700±1370; 6.6±0.5, respectively) and in CKD+NAC (91.4±5; 0.6±0.02; 126±7.5; 73±6; 51±3.5; 24,720±1,114; 10,080±748; 4.5±0.5, respectively) in comparison to C (41±0.9; 0.4±0.03; 76±2.7; 51.5±3; 14±0.9; 21,750±960; 5,314±129; 2±0.2, respectively; p<0.001) and C+NAC (40±0.9; 0.3±0.02; 76±2.6; 68±4; 18.4±1.5; 20,040±700; 5,050±267; 1.8±0.2, respectively; p<0,001). TC, urea, creatinine, total AGE, pentosidine and TBARS were respectively, 17%, 25%, 33%, 24%, 40% and 28% (p<0.01) lower in CKD+NAC, than in CKD. Glycemia was higher in C+NAC (107±4.6) and CKD+NAC (107±2.6) than in C (96±1.8; p<0.05) and CKD (98±1.6; p<0.01), respectively. In macrophages (n=6), CKD albumin increased PDI (5 and 7 times, p<0.01) and Grp94 (66% and 80%, p<0.01) in comparison to C and CKD+NAC-albumin treated cells, respectively. Conclusion: NAC reduces plasma lipid peroxidation and AGE and abrogates ERS induced by CKD-albumin. This may contribute to attenuate the deleterious effects of CKD-albumin on lipid accumulation in macrophages helping preventing atherogenesis in CKD.

Effect of N-acetylcysteine on apoptosis-related gene programmed cell death 5 of myocardium in rats after overtraining

Objective To study the influence of N-acetylcysteine (NAC) on myocardial apoptosis-related gene programmed cell death 5 (PDCD5) expression in rat overtraining model.Methods Thirtysix male Wister rats were randomly divided into three groups:control group (group C,n =12),overtraining group (group O,n =12) and overtraining with administration of NAC group (group N,n =12).The animal model was developed by seven-week repeated exhaustive swimming stress.Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) and Western blotting were used to detect changes of PDCD5 mRNA expression and changes of cytochrome C (Cyclin C) protein exression respectively in myocardium of rats.Serum level of Troponin Ⅰ Type 3 (TNNI3) was measured by using enzyme linked immunosorbent assay (ELISA).Results As compared with group C,the expression of PDCD5 mRNA and Cyclin C protein in rat myocardium and the content of serum TNNI3 were significantly increases in group O [PDCD5 mRNA:2.297±0.098 vs.1.060 ±0.065; Cyclin C:0.485 ±0.161 vs.0.327 ±0.120; TNNI3:(198.107 ±12.060) ng/L vs.(84.854 ± 11.574) ng/L] (P ＜ 0.01) ; but after being interfered with NAC,the expression of PDCD5 mRNA and Cyclin C protein in rat myocardium and the content of serum TNNI3 were significantly lowered in group N vs.group O [PDCD5:1.739 ± 0.065 vs.2.297 ± 0.098 ; Cyclin C:0.381 ± 0.326 vs.0.485±0.161; TNNI3:(128.265 ±11.489) ng/L vs.(198.107±12.060) ng/L] (P＜0.01),and higher than in group C [PDCD5 mRNA:1.060 ± 0.065 ; Cyclin C:0.327 ± 0.120 ; TNNI3:(84.854 ± 1 1.574) ng/L] (P ＜ 0.01).Conclusion NAC can prevent myocardial damage induced by overtraining via down-regulating the PDCD5 mRNA expression and inhibiting cytochrome C released from mitochondria. Key words: N-acetylcysteine; Programmed cell death 5; Overtraining; Apoptosis

Influence of N-Acetylcysteine on Klotho Expression and Its Signaling Pathway in Experimental Model of Chronic Cyclosporine Nephropathy in Mice

Cyclosporine A (CsA)-associated oxidative stress has been proposed as an important mechanism of renal injury. This study was designed to examine whether N-acetylcysteine (NAC), a well-known antioxidant, affects Klotho, antiaging gene, expression and its signaling pathway in an experimental model of chronic CsA nephropathy. Mice maintained on a low-sodium diet were given vehicle (olive oil, 1 mL/kg/day), CsA (30 mg/kg/day), NAC (150 mg/kg/day), or a combination of CsA and NAC for 4 weeks. The effect of NAC on CsA-induced renal injury was evaluated with basic parameters, histopathology, and markers of oxidative stress [8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion and manganese superoxide dismutase (MnSOD) expression]. The influence of NAC on Klotho and its signal pathway (p-AKT and p-FoxO1) in CsA-treated mouse kidney was evaluated with immunohistochemistry and/or immunoblot. Concomitant administration of CsA and NAC significantly improved renal function and attenuated tubulointerstitial fibrosis, and these changes were accompanied by decreased urinary 8-OHdG level and increased MnSOD expression. NAC treatment preserved Klotho gene expression compared with CsA treatment alone (P < 0.05), and this correlated with urinary 8-OHdG excretion (r = -0.934) and MnSOD expression (r = 0.873, P < 0.001 for both). Concomitant treatment of CsA and NAC translocated FoxO1 from the cytoplasm to the nucleus, implicating dephosphorylation of FoxO1 by NAC in p-AKT/p-FoxO1 pathway. NAC treatment preserves Klotho expression and modifies p-AKT/p-FoxO1 pathway in chronic CsA nephropathy.

Cytotoxicity of single-walled carbon nanotubes to human lung carcinoma cells: The influence of N-acetylcysteine

Background: Single-walled carbon nanotubes (SWCNTs) have been reported to induce cytotoxicity in different cell lines. Although the mechanisms underlying cytotoxicity are not fully understood, accumulation of reactive oxygen species (ROS) and oxidative damage is considered to be a likely contributing factor. Methods: Human lung carcinoma cells, A549, and human fetal lung fibroblasts, MRC-5 were used to assess the cytotoxicity of SWCNT in the presence and absence of a redox status regulator, N-acetylcysteine (NAC), via the MTT assay. Results: SWCNT induced a nearly three-fold greater loss of viability in A594 vs. MRC-5 cells at ?250 ?g/ml. SWCNT cytotoxicity at higher concentrations was similar for both cell lines, while NAC alone was non-toxic. The cytotoxicity of SWCNT (250 ?g/ml) in combination with NAC to A549 cells was significantly decreased at the lowest NAC concentration (1.5 ?g/ml), and was similar to NAC treatment alone at that concentration. Higher concentrations of NAC in combination with SWCNT (250 ?g/ml) resulted in increased cytotoxicity in both A549 and MRC-5 cells. Conclusion: A549 malignant lung cells are more susceptible to low concentrations of SWCNT vs. normal lung cells, and low concentrations of N-acetylcysteine appear to be cytoprotective, possibly due to its antioxidant properties.

Hematological indices and activity of NTPDase and cholinesterase enzymes in rats exposed to cadmium and treated with N-acetylcysteine

The present study aimed to investigate the influence of N-acetylcysteine (NAC) on cadmium (Cd) poisoning by evaluating Cd concentration in tissues, hematological indices as well as the activity of NTPDase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes of rats exposed to Cd and co-treated with NAC. For this purpose, the rats received Cd (2 mg/kg) and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided into four groups (n = 6-8): control/saline, NAC, Cd, and Cd/NAC. Cd exposure increased Cd concentration in plasma, spleen and thymus, and NAC co-treatment modulated this augment in both lymphoid organs. Cd exposure reduced red blood cell count, hemoglobin content and hematocrit value. Cd intoxication caused a decrease in total white blood cell count. NAC treatment per se caused an increase in lymphocyte and a decrease in neutrophil counts. On contrary, Cd exposure caused a decrease in lymphocyte and an increase in neutrophil and monocyte counts. NAC reversed or ameliorated the hematological impairments caused by Cd poisoning. There were no significant alterations in the NTPDase activity in lymphocytes of rats treated with Cd and/or NAC. Cd caused a decrease in the activities of lymphocyte AChE, whole blood AChE and serum BChE. However, NAC co-treatment was inefficient in counteracting the negative effect of Cd in the cholinesterase activities. The present investigation provides ex vivo evidence supporting the hypothesis that Cd induces immunotoxicity by interacting with the lymphoid organs, altering hematological parameters and inhibiting peripheral cholinesterase activity. Also, it highlights the possibility to use NAC as adjuvant against toxicological conditions.

Influence of N-Acetyl cysteine on selected extrapyramidal movement disorders and oxidative stress induced by haloperidol in rats

Haloperidol (HAL) is a widely used neuroleptic drug for the treatment of acute and chronic psychosis. Its use is limited by its tendency to produce a range of extrapyramidal movement disorders such as, tardive dyskinesia (TD), akathisia, dystonia and parkinsonism. Increased levels of thiobarbituric-acid reactive products have been found inthe cerebrospinal fluid and plasma of patients treated with neuroleptics, especially those with movement disorders. HAL, is metabolized by an oxidase, generates large quantities of oxyradicals and a potent toxic pyridinium-like metabolite and induces oxidative stress. It is proposed to study the effect of n-acetyl cysteine (NAC) on selected extrapyramidal movement disorders (tardive dykinesia and catalepsy), total antioxidant status and lipid peroxidation induced by HAL. HAL (1 mg/kg/i.p) was injected for 21 days in rats, and NAC at doses of 30, 100 and 300 mg/kg dissolved in normal saline was administered,intra-peritoneally once (30 minutes prior to haloperidol) on the last day of HAL treatment. NAC supplementation significantly decreased haloperidol induced TD and catalepsy dose dependently. However, further work is required to investigate the effect of chronicadministration of NAC in the improvement of TD so as to confirm the usefulness of NAC assupplements for improved control of TD.

Effects of N-acetylcysteine and ebselen on arachidonic acid release from astrocytes and neurons cultured in normoxic or simulated ischemic conditions

Arachidonic acid (AA) is released from cells after nervous tissue injuries. We treated rat cortical neurons and astrocytes cultured under normoxic or simulated ischemic conditions with N-acetylcysteine (100 or 200M) or ebselen (10 or 20M). N-acetylcysteine decreased AA release in normoxic astrocytes, while ebselen decreased AA release from astrocytes in both conditions. N-acetylcysteine produced no changes in neuronal AA release. A low dose of ebselen significantly increased AA release from neurons in both conditions. The influence of N-acetylcysteine and ebselen on AA release might be implicated in their effects on astrocytes and neurons, however, the exact mechanisms have yet to be explained.

Regulation of CYP4A expression by bezafibrate in primary culture of rat and human hepatocytes: Interspecies difference and influence of N-acetylcysteine

The effects of fibrates on cytochrome P450 4A (CYP4A) expression have not been clearly evaluated in human hepatocytes, human being reported as a non-responsive species. We have evaluated the effects of clofibrate, bezafibrate (BEZA), WY-14643, nafenopin and ciprofibrate at the concentration of 250 μM on CYP4A expression in primary cultures of rat and human hepatocytes. BEZA greatly induced mRNA expression in both species. Eight out of 10 human cultures responded to BEZA 250 μM. CYP4A-dependent activity was increased in rat, but not in human hepatocytes. The antioxidant N-acetylcysteine (Nac) enhanced the inducing effect of BEZA on mRNA expression, this potentialization being higher in human compared to rat hepatocytes. By contrast, Nac decreased the inducing effect of BEZA on CYP4A-dependent activity in rat and had either no effect or decreased the activity in BEZA-treated human hepatocytes. In conclusion, the cellular environment appears as an important parameter to take into account when studying CYP4A induction and could partly explain interspecies differences in the complex regulation of CYP4A expression.