Combination Of N-acetylcysteine Research Articles

A combination of levosimendan and N-Acetylcysteine shows significant favorable efficacy on experimental liver ischemia/reperfusion injury.

Ischemia-reperfusion injury (IRI) is cellular damage that emerges from re-oxygenation of a hypoxic organ. In the present study, we aimed to examine the effects of a combination of levosimendan, an inotropic agent, and N-Acetylcysteine, the precursor of antioxidants and glutathione, in an experimental liver IRI model. In this study, 38 rats were randomly divided into five groups. Before the ischemia, study arms were given physiological saline solution, N-Acetylcysteine (NAS), levosimendan or a combination of NAS+levosimendan in a predetermined amount and duration, and the infusion was continued until the end of this study. The hepatic pedicle was occluded using an atraumatic vein clamp, and 60 minutes of ischemia was achieved. The clamp was then opened and 60 minutes of reperfusion was ensured. Liver tissue samples were obtained after sacrifice, and tissue malondialdehyde (MDA) and myeloperoxidase (MPO) levels were determined. Serum Tumor Necrosis Factor (TNF)-α, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and MPO levels of blood samples were also measured. Among the histopathological changes in the liver tissue after IRI, differences between groups were statistically significant in the injury scoring system based on congestion, vacuolization and necrosis levels. Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage. The use of a levosimendan plus NAS combination in liver IRI markedly suppressed inflammation and oxidative stress and significantly reduced liver ischemia-reperfusion injury and can be recommended for decreasing IRI instead of single agent use of levosimendan or NAS.

Antiproliferative and apoptotic interaction between azathioprine and N-acetylcysteine in acute lymphoblastic leukemia Jurkat cells

Abstract T cell acute lymphoblastic leukaemia is a type of cancer that develops from lymphoid progenitors, and chemotherapy is corner stone of the treatment. Thiopurine drugs, consisting of 6-mercaptopurine, 6-thioguanine, and azathioprine (Aza), can effectively treat this disease. To be activated, Aza must first be biotransformed to 6-mercaptopurine by thiol groups in glutathione. However, glutathione is decreased in cancer cells due to high levels of reactive oxygen species (ROS). N-acetylcysteine could provide thiol groups for glutathione synthesis to biotransform Aza. Using flow cytometry, the ability of N-acetylcysteine to increase the antiproliferative and apoptotic effects of Aza without increasing ROS was tested in Jurkat cells. Individually, Aza 1.0 and 2.0 μM, as well as N- acetylcysteine 3.0 mM, induced apoptosis and cell cycle arrest. Together, Aza + N-acetylcysteine significantly reduced proliferation compared to that obtained with the individual drugs. Combination of N-acetylcysteine 3.0 mM with Aza 1.0 μM was as effective at inducing apoptosis as Aza 2.0 μM alone. The combination of N-acetylcysteine 3.0 mM + Aza 1.0 μM increased cell cycle arrest at the G2/M phase. We found that Aza 1.0 or 2.0 μM induced a significant increase in ROS compared to that in untreated cells, while N-acetylcysteine 3.0 mM and N-acetylcysteine 3.0 mM + Aza 1.0 μM kept ROS at control levels; the latter drugpairing represents a favourable combination to reduce oxidative stress in the presence of Aza. In conclusion, N-acetylcysteine augments antiproliferative and apoptotic effects of Aza without increasing ROS in vitro.

N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli.

Fluoroquinolones such as ciprofloxacin induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS). Both the SOS response and ROS increase bacterial mutagenesis, fuelling the emergence of resistant mutants during antibiotic treatment. Recently, there has been growing interest in developing new drugs able to diminish the mutagenic effect of antibiotics by modulating ROS production and the SOS response. To test whether physiological concentrations of N-acetylcysteine, a clinically safe antioxidant drug currently used in human therapy, is able to reduce ROS production, SOS induction and mutagenesis in ciprofloxacin-treated bacteria without affecting antibiotic activity. The Escherichia coli strain IBDS1 and its isogenic mutant deprived of SOS mutagenesis (TLS-) were treated with different concentrations of ciprofloxacin, N-acetylcysteine or both drugs in combination. Relevant parameters such as MICs, growth rates, ROS production, SOS induction, filamentation and antibiotic-induced mutation rates were evaluated. Treatment with N-acetylcysteine reduced intracellular ROS levels (by ∼40%), as well as SOS induction (by up to 75%) and bacterial filamentation caused by subinhibitory concentrations of ciprofloxacin, without affecting ciprofloxacin antibacterial activity. Remarkably, N-acetylcysteine completely abolished SOS-mediated mutagenesis. Collectively, our data strongly support the notion that ROS are a key factor in antibiotic-induced SOS mutagenesis and open the possibility of using N-acetylcysteine in combination with antibiotic therapy to hinder the development of antibiotic resistance.

Combined N-Acetylcysteine and Clomiphene Citrate for Ovulation Induction in Polycystic Ovary Syndrome, a Double Blind Randomized Controlled Trial

Combined N-Acetylcysteine and Clomiphene Citrate for Ovulation Induction in Polycystic Ovary Syndrome, a Double Blind Randomized Controlled Trial

Effect of N-Acetyl cysteine and Pomegranate Peel Water Extract on Hepatotoxicity Induced by Paracetamol.

Background: One of the safest antipyretics, analgesics is paracetamol when used at therapeutic doses but overdoses caused hepatic necrosis. Recent researches were proven the ability of pomegranate to treat many diseases. For new ways to reduce paracetamol toxicity pomegranate peel extract was used in comparison to N- Acetyl cysteine a standard antidote for paracetamol toxicity. Methods: Seventy two adult male albino rats were divided equally into nine groups; Negative control group; Solvent )distilled water) group; N-Acetyl cysteine treated group (a single dose 150 mg/kg. B.w/day orally); Pomegranate peel extract treated group (a single dose 430mg/kg. b. W/ day orally); N-Acetyl cysteine and Pomegranate peel extract treated group (each rat was given same previous doses); Paracetamol group (a single dose of 400 mg/ kg. B.w / day orally); N-Acetyl cysteine; Pomegranate peel extract and combination of N-Acetyl cysteine and Pomegranate peel extract with paracetamol were three treatment groups received the same previous doses. Treatment Continued for 28 days. These samples were collected for matrix metalloproteinase assessment in blood serum; Hepatic antioxidants and Oxidative stress marker assessment in plasma and liver tissue homogenates and Routine liver injury marker assessment in blood serum. Res49ults: Treatment with paracetamol caused hepatic toxicity, the Pomegranate peel extract showed a mild hepatoprotective effect, N-acetyl cysteine showed the moderate hepatoprotective effect and combination treatment of N-Acetyl cysteine and Pomegranate peel extract showed the best hepatoprotective effect against paracetamol toxicity. Conclusion: Paracetamol is a hepatotoxic and combination of N-Acetyl cysteine and the Pomegranate peel extract is the best treatment against Paracetamol hepatic toxicity.

Effectiveness of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain in the treatment of endometriosis-associated pelvic pain: LEAP study

ObjectiveTo assess the impact of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain on endometriosis-associated pelvic pain. Study designMulticenter, open-label, non-comparative clinical trial in a representative sample of women with endometriosis-associated pelvic pain. ResultsIn total, 398 patients with a mean age of 34.6 ± 7.2 years were treated with a combination of N-acetyl cysteine, alpha lipoic acid and bromelain for 6 months. At baseline, 92.7% of the patients had pain intensity > 4 on the visual analogue scale (VAS); at 3 months of treatment, this percentage decreased to 87.2% (p = 0.074) and at 6 months the percentage was 82.7% (p < 0.05). ConclusionsWomen with endometriosis who wish to become pregnant and are treated with a preparation containing N-acetyl cysteine, alpha lipoic acid and bromelain experienced a significant improvement in endometriosis-associated pelvic pain and required lower intake of rescue analgesics.

The effect of N-acetylcysteine on mechanical fatigue resistance of antibiotic-loaded bone cement

BackgroundThis biomechanical study evaluates the effect of N-acetylcysteine alone and in combination with the most commonly used antibiotic-loaded bone cement mixtures.MethodsWe mixed eight bone cement mixture groups including combinations of N-acetylcysteine, gentamicin, teicoplanin, and vancomycin and applied a four-point bending test individually to each sample on days 1 and 15 using an MTS Acumen test device.ResultsThe result was less than 50 MPa—the limit declared by the ISO (International Standards Organization)—in only the “gentamicin + bone cement + N-acetylcysteine” group. Mechanical fatigue resistance of the bone cement decreased significantly with the addition of N-acetylcysteine both on day 1 and day 15 (p < 0.001). With the addition of N-acetylcysteine into the “gentamicin + bone cement” and “vancomycin + bone cement” mixtures, a significant decrease in mechanical fatigue resistance was observed both on day 1 and day 15 (p < 0.001). In contrast, with the addition of N-acetylcysteine into the “teicoplanin + bone cement” mixture, no significant difference in mechanical fatigue resistance was observed on days 1 and 15 (p = 0.093, p = 0.356).ConclusionPreliminary results indicate that adding N-acetylcysteine to teicoplanin-loaded bone cement does not significantly affect the cement’s mechanical resistance, potentially leading to a new avenue for preventing and treating peri-prosthetic joint infection. N-acetylcysteine may, therefore, be considered as an alternative agent to be added to antibiotic-loaded bone cement mixtures used in the prevention of peri-prosthetic joint infection.

In vitro synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii grown in planktonic phase and in biofilms.

ObjectivesTo investigate the potential synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii strains grown in planktonic phase or as biofilms.MethodsSixteen strains were investigated, including nine colistin-susceptible (MIC range 0.5–1 mg/L) and seven colistin-resistant (MIC range 16–256 mg/L) strains. Synergism of colistin in combination with N-acetylcysteine was investigated by chequerboard assays. The activity of colistin/N-acetylcysteine combinations was further evaluated by time–kill assays with planktonic cultures (three colistin-resistant strains and one colistin-susceptible strain) and by in vitro biofilm models (three colistin-resistant and three colistin-susceptible strains).ResultsChequerboard assays revealed a relevant synergism of colistin/N-acetylcysteine combinations with all colistin-resistant strains, whereas no synergism was observed with colistin-susceptible strains. Time–kill assays showed a concentration-dependent potentiation of colistin activity by N-acetylcysteine against colistin-resistant strains, with eradication of the culture by combinations of N-acetylcysteine at 8000 mg/L plus colistin at 2 or 8 mg/L. A static effect during the first 8 h of incubation was demonstrated with the colistin-susceptible strain exposed to 0.25 × MIC colistin plus 8000 mg/L N-acetylcysteine. A remarkable antibiofilm synergistic activity of 8 mg/L colistin plus 8000 mg/L N-acetylcysteine was demonstrated with all colistin-resistant and colistin-susceptible strains. The effects were greater with colistin-resistant strains (marked reduction of viable biofilm cells was observed at sub-MIC colistin concentrations).Conclusions N-acetylcysteine, at concentrations achievable by topical administration, was shown to revert the colistin-resistant phenotype in A. baumannii, and to exert a relevant activity against biofilms of colistin-susceptible and colistin-resistant A. baumannii strains.

Controlling of apoptosis and proliferation of HepG2 cancer cells by treatment of plasma jet and N-acetylcysteine combination

It is well known that atmospheric pressure plasma could induce apoptosis of cancer cells. [1][2] However, the interaction and mechanism between plasma and cancer cells has not been fully understood yet. [3] Here, we report the controlment of apoptosis and proliferation of human hepatocellular carcinoma cell (HepG2) by combined treatment of He/O2 plasma jet and N-acetylcysteine (NAC, free radical scavenger). It is found that the fate of HepG2 cells could be controlled by plasma treatment time together with NAC pretreatment. Pure plasma treatment could induce apoptosis of HepG2 cells. However, on one hand, 15s plasma with NAC pre-treatment could enhance proliferation of HepG2 cell as a function of NAC concentration. On the other hand, NAC-pretreatment could markedly compromise apoptosis effect by long time plasma treatment (e.g. >240s) without proliferation observed. The NAC and 15s plasma treatment accelerates the G1 to S phase transition of HepG2 cells causing proliferation while long time plasma treatment arrests the cell cycle at the G2/M phase inducing apoptosis.

In vitro effects of N-acetylcysteine alone and combined with tigecycline on planktonic cells and biofilms of Acinetobacter baumannii.

Acinetobacter baumannii (A. baumannii), as a common opportunistic pathogen, has strong ability to form biofilms, which has led to drug resistance and chronic infections. The combination of N-acetylcysteine (NAC) and tigecycline (TGC) was demonstrated to synergistically inhibit biofilm-associated bacterial infections, including methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. The purpose of this study is to investigate the effect of NAC and TGC on planktonic cells and biofilms of A. baumannii. Minimum inhibitory concentrations (MICs) of NAC were determined by broth microdilution method. Biofilm susceptibility was assessed by crystal violet stain. Interactive effects of NAC and TGC on planktonic cells were determined by checkerboard MIC assay. Viable cell count was used to evaluate the combined effect of NAC and TGC on biofilm-embedded bacteria. MICs of NAC against 25 A. baumannii isolates ranged from 16 to 128 mg/mL. NAC alone (0.5-128 mg/mL) significantly inhibited biofilm formation and disrupted preformed biofilms. The combination of NAC and TGC induced a partial synergistic effect (60%) and additive effect (28%) on planktonic bacteria. For biofilm-embedded bacteria, treatment with 16 mg/mL NAC alone or 2 µg/mL TGC alone resulted in significant bactericidal effects (P<0.01 and P<0.05, respectively); synergistic bactericidal effect was found at 4 mg/mL NAC combined with 0.5 µg/mL TGC (P<0.01). NAC alone significantly inhibited biofilm formation of A. baumannii. The combination of NAC and TGC induced partial synergistic effect against planktonic cells and synergistic effect against biofilm-embedded A. baumannii, which might be a therapeutic option for biofilm-related infections of A. baumannii.

Oxidative stress mediates an increased formation of vascular endothelial growth factor in human hepatocarcinoma cells exposed to erlotinib.

The tyrosine kinase inhibitor erlotinib targets the receptor of epidermal growth factor (EGFR) involved in development of hepatocellular carcinoma (HCC).Although inefficient in established HCC, erlotinib has been recently proposed for HCC chemoprevention. Since Cyp3A4 and Cyp1A2 enzymes metabolize erlotinib in the liver, the insights into the mechanisms of erlotinib effects on liver cells with maintained drug metabolizing activity are needed.We applied erlotinib to both commercially available (SNU398, Huh7) and established in Austria HCC cell lines (HCC-1.2, HCC-3). Cyp3A4 and Cyp1A2, microarray gene expression, cell viability, LDH release, DHFC fluorescence were assessed. VEGF expression was analysed by real-time RT-PCR and ELISA.Higher cumulative expression of erlotinib metabolizing enzymes was observed in HCC-1.2 and HCC-3 cells. Gene expression microarray analysis showed upregulation of VEGF signalling by erlotinib. VEGF was increased up to 134 ± 14% (n = 5, p = 0.002) in HCC-1.2, HCC-3 and Huh7 cells. Interventions by Cyp1A2 and Mek2siRNA, MEK inhibitor UO126, diphenylene iodonium, as well as a combination of N-acetylcysteine with selenium all inhibited VEGF upregulation caused by erlotinib.Thus, erlotinib increases VEGF production by mechanisms involving Cyp1A2, oxidative stress and MEK1/2. VEGF may favour angiogenesis and growth of early HCC tumours limiting the therapeutic and chemopreventive effects of erlotinib.

Combination of tauroursodeoxycholic acid and N-acetylcysteine exceeds standard treatment for acetaminophen intoxication.

Acetaminophen overdose in mice is characterized by hepatocyte endoplasmic reticulum stress, which activates the unfolded protein response, and centrilobular hepatocyte death. We aimed at investigating the therapeutic potential of tauroursodeoxycholic acid, a hydrophilic bile acid known to have anti-apoptotic and endoplasmic reticulum stress-reducing capacities, in experimental acute liver injury induced by acetaminophen overdose. Mice were injected with 300mg/kg acetaminophen, 2hours prior to receiving tauroursodeoxycholic acid, N-acetylcysteine or a combination therapy, and were euthanized 24hours later. Liver damage was assessed by serum transaminases, liver histology, terminal deoxynucleotidyl transferase dUTP nick end labelling staining, expression profiling of inflammatory, oxidative stress, unfolded protein response, apoptotic and pyroptotic markers. Acetaminophen overdose resulted in a significant increase in serum transaminases, hepatocyte cell death, unfolded protein response activation, oxidative stress, NLRP3 inflammasome activation, caspase 1 and pro-inflammatory cytokine expressions. Standard of care, N-acetylcysteine and, to a lesser extent, tauroursodeoxycholic treatment were associated with significantly lower transaminase levels, hepatocyte death, unfolded protein response activation, oxidative stress markers, caspase 1 expression and NLRP3 levels. Importantly, the combination of N-acetylcysteine and tauroursodeoxycholic acid improved serum transaminase levels, reduced histopathological liver damage, UPR-activated CHOP, oxidative stress, caspase 1 expression, NLRP3 levels, IL-1β levels and the expression of pro-inflammatory cytokines and this to a greater extend than N-acetylcysteine alone. These findings indicate that a combination strategy of N-acetylcysteine and tauroursodeoxycholic acid surpasses the standard of care in acetaminophen-induced liver injury in mice and might represent an attractive therapeutic opportunity for acetaminophen-intoxicated patients.

The combination of N-acetylcysteine with fibrinolytic therapy in patients with acute coronary syndrome

Objectives: The aim of our study combination therapy N-acetylcystein with fibrinolytic therapy in patients with acute coronary syndrome

N-Acetylcysteine in Combination with IGF-1 Enhances Neuroprotection against Proteasome Dysfunction-Induced Neurotoxicity in SH-SY5Y Cells

Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson's disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 activation, and nuclear condensation and fragmentation. In addition, MG132 treatment leads to endoplasmic reticulum (ER) stress and autophagy-mediated cell death. All of these events can be attenuated without obvious reduction of MG132 induced protein ubiquitination by first treating the cells with NAC and IGF-1 separately or simultaneously prior to exposure to MG132. Moreover, our data demonstrated that the combination of the two proved to be significantly more effective for neuronal protection. Therefore, we conclude that the simultaneous use of growth/neurotrophic factors and a free radical scavenger may increase overall protection against UPS dysfunction-mediated cytotoxicity and neurodegeneration.

The Effect of N-acetylcysteine on Pyrrolized Protein, Lipid Hydroperoxide and Thiol Levels in the Carbon Tetrachloride Hepatotoxicity

This study was performed, on the rat model, to form oxidative stress by carbon tetrachloride (CCl4) and to reveal the relationship between toxicity and oxidative/thiol stresses through lipid/protein oxidation and to investigate the effects of N-acetylcysteine on the hepatotoxicity induced oxidative stress. Wistar albino male rats were divided into four groups as CCl4, N-acetylcysteine, CCl4-N-acetylcysteine and Control, each of ten rats. CCl4 (1.0 ml, 800 mg/kg; single dose) and N-acetylcysteine (200 mg; three doses) were intraperitoneally applied to corresponding groups as per kg of rat weight. Hepatotoxicity was identified with histopathological methods. Besides the thiol levels in plasma/tissue samples, pyrrolized protein and total lipid hydroperoxide levels in serum samples were measured. CCl4-induced hepatotoxic lesions remarkably improved in the presence of N-acetylcysteine. There was no significant difference between Control and N-acetylcysteine groups, in terms of parameters measured in serum/plasma and tissue samples. When compared to these groups, pyrrolized protein and total lipid hydroperoxide levels were found to be higher; whereas plasma/tissue thiol levels lower in the CCl4 group. N-acetylcysteine in combination with CCl4 significantly lowered pyrrolized protein and total lipid hydroperoxide levels, and increased thiol levels, so that the values were reached to those of Control and N-acetylcysteine groups. As reflected by higher pyrrolized protein and total lipid hydroperoxide, and lower thiol levels, enhanced free radical production in the CCl4 hepatotoxicity may lead to oxidative and thiol stresses mediated lipid/protein oxidation. In addition, N-acetylcysteine, a powerful antioxidant, may be added as a thiol source to the treatment protocols of several diseases whose pathogenesis is of oxidative and thiol stress.

Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial.

BackgroundN-acetylcysteine (NAC) has been used as a classic treatment for hepatotoxicity induced by N-acetyl-p-benzoquinone imine (NAPQI) as a metabolite of acetaminophen. However, cimetidine theoretically can reduce the production of toxic metabolites through the inhibition of cytochrome p450, and it recently was proposed as a complementary treatment for acetaminophen toxicity.ObjectiveThe aim of this study was to compare the effects of treating acute acetaminophen toxicity with NAC alone and with a combination of NAC and cimetidine.MethodsFrom October 2013 to March 2014, 105 patients suspected of acetaminophen toxicity who had paraclinical confirmation of toxicity requiring medical treatment (based on the risk assessment nomogram of acetaminophen serum level) were enrolled in this double-blind, randomized, controlled trial at Imam Reza Hospital in Mashhad, Iran. The patients were divided into two groups, i.e., 1) patients who were treated with NAC alone (group A) and 2) patients who were treated with a combination of NAC and cimetidine (group B). The primary outcomes were 1) the serum level of acetaminophen and 2) the serum level of aminotransferases at the time of admission and 4, 12, 24, and 48 hours after admission. Exclusion criteria included multiple toxicities, concurrent diseases that could affect liver enzymes, the use of other drugs, and dissatisfaction with the project. For measuring quantitative data, SPSS version 16 was used for t-test analysis and for analyzing the qualitative data with chi-squared analysis.ResultsSixty patients (32 females and 28 males) with a mean age of 25.2 ± 7.3 years were classified in two groups of 30.. There was no difference between the groups in terms of their admission information. The average levels of acetaminophen in both groups at admission, 12, 24, and 48 hours after hospitalization were not significantly different from each other. Twelve hours after hospitalization, the aspartate aminotransferase (AST) level in the group treated with NAC was significantly higher than in the group treated with the combination of NAC and cimetidine (IU/L30.1 ± 110.0 versus IU/L26.38 ± 94.93, p = 0.044). At the other times that the level of liver enzymes was assessed, the serum levels of urea and creatinine were not significantly different in the two groups (p > 0.05)ConclusionThe intravenous administration of 300 mg of cimetidine every six hours with NAC did not improve the level of hepatoprotective action significantly compared with the NAC treatment protocol alone.

Multiple mechanisms of age-dependent accumulation of amyloid beta protein in rat brain: Prevention by dietary supplementation with N-acetylcysteine, α-lipoic acid and α-tocopherol

The aged brain may be used as a tool to investigate altered metabolism of amyloid beta protein (Aβ42) that may have implications in the pathogenesis of Alzheimer's disease (AD). In the present study, we have observed a striking increase in the amyloid precursor protein (APP) level in the brain cortex of aged rats (22–24 months) along with a mild but statistically significant increase in the level of APP mRNA. Moreover, the activity of β secretase is elevated (nearly 55%) and that of neprilysin diminished (48%) in brain cortex of aged rats compared to that in young rats (4–6 months). All these changes lead to a markedly increased accumulation of Aβ42 in brain cortical tissue of aged rats. Long-term dietary supplementation of rats with a combination of N-acetylcysteine, α-lipoic and α-tocopherol from 18 months onwards daily till the sacrifice of the animals by 22–24 months, attenuates the age-related alterations in amyloid beta metabolism. In separate experiments, a significant impairment of spatial learning and memory has been observed in aged rats, and the phenomenon is remarkably prevented by the dietary supplementation of the aged animals by the same combination of N-acetylcysteine, α-lipoic acid and α-tocopherol. The results call for further explorations of this combination in suitable animal models in ameliorating AD related brain deficits.

Effect of N-acetylcysteine and allopurinol combination to protect spinal cord ischemia/reperfusion injury induced by aortic cross-clamping in rat model.

PurposeThe aim of this experimental study was to determine whether combination of N-acetylcysteine and allopurinol can reduce the ischemia/reperfusion injury of spinal cord in a rat model.MethodsTwenty-seven Spraque Dawley rats, all male, weighing between 220 to 370 (mean 325) gr were used in the study. 27 rats were divided into three groups: sham group, control group and experimental group. Abdominal aortic occlusion between the renal arteries and iliac bifurcations was carried out for 60 min with proximal and distal clip in control and experimental groups. Hindlimb motor functions were evaluated at 24, and 48 h using the Tarlov Scale. Besides, spinal cord samples were taken for determination of superoxide dismutase, and catalase activities as antioxidant enzymes, and malondialdehyde as an indicator of lipid peroxidation and xanthine oxidase levels as source hydroxyl radical for biochemical studies. Also, histopathological evaluation was made from cord tissue samples.ResultsThe experimental group subjects had better neurological functions than control group subjects. In experimental group; superoxide dismutase and catalase levels increased, while malondialdehyde and xantine oxidase levels decreased as compared with control group. Histopathological examination showed that experimental group had less cell degeneration, hemorrhage, edema and inflammation loss than control group.ConclusionsThis study offers that combined use of N-acetylcysteine and allopurinol might help protect the spinal cord against ischemia/reperfusion injury.

Effect of L-arginine in combination with N-acetylcysteine on oxidative stress and left ventricular function in patients with acute coronary syndrome with st segment elevation

The aim of this study was to evaluate the effect of treatment on L-arginine (LA) with a combination of N-acetylcysteine (NAC) on oxidative stress, infarct size, and left ventricular (LV) as adjunctive therapy in acute coronary syndrome (ACS). Patients with ACS received either 15 g NAC infused over 24 h (n = 15) or no NAC (n = 15), combined with LA. Peripheral venous blood was serially sampled to measure creatine kinase (CK)-MB levels. Plasma malondialdehyde (MDA) level was measured at admission and after 4 and 24 h. Echocardiography was performed within 3 days of MI and after 3 months. In the NAC-treated patients plasma MDA levels decreased, whereas in the nontreated NAC patients MDA levels increased at 4 and 24 h (P < 0.01 and P < 0.001, respectively). Left ventricular ejection fraction was higher (P < 0.05) and LV end-systolic and end-diastolic diameters were lower (P < 0.001 and P < 0.001) in patients receiving NAC on day 3. Left ventricular wall motion score index was significantly lower in patients treated with NAC on day 3 (P < 0.05). Left ventricular diastolic parameters were not different whether patients were treated with NAC or not. No difference in reduction of infarct size was detected between the groups according to CK-MB levels. It was thus demonstrated that administration of NAC in combination with LA significantly diminished oxidative stress and improved LV function in patients with ACS. These encouraging results would justify the performance of a larger controlled study.

The combination of N-acetylcysteine with nitroglycerin in the treatment of acute coronary syndrome with st segment elevation

The combination of N-acetylcysteine with nitroglycerin in the treatment of acute coronary syndrome with st segment elevation